mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Bio-Humoral and Non-Invasive Haemodynamic Correlates of Renal Venous Flow Patterns across the Heart Failure Spectrum.

Background: We evaluated the bio-humoral and non-invasive haemodynamic correlates of renal congestion evaluated by Doppler renal venous flow (RVF) across the heart failure (HF) spectrum, from asymptomatic subjects with cardiovascular risk factors (Stage A) and structural heart disease (Stage B) to patients with clinically overt HF (Stage C). Methods: Ultrasound evaluation, including echocardiography, lung ultrasound and RVF, along with blood and urine sampling, was performed in 304 patients. Results: Continuous RVF was observed in 230 patients (76%), while discontinuous RVF (dRVF) was observed in 74 (24%): 39 patients had pulsatile RVF, 18 had biphasic RVF and 17 had monophasic RVF. Stage C HF was significantly more common among patients with dRVF. Monophasic RVF was associated with worse renal function and a higher urinary albumin-to-creatinine ratio (uACR). After adjusting for hypertension, diabetes mellitus, the presence of Stage C HF and serum creatinine levels, worsening RVF patterns were associated with higher NT-proBNP levels, worse right ventricular-arterial coupling, larger inferior vena cava and higher echo-derived pulmonary artery wedge pressure. This trend was confirmed when only patients with HF Stage C were analysed after adjusting for the left ventricle ejection fraction (LVEF). Conclusion: Abnormal RVF is common across the HF spectrum. Worsening RVF patterns are independently associated with increased congestion, worse non-invasive haemodynamics and impaired RV-arterial coupling. RVF evaluation could refine prognostic stratification across the HF spectrum, irrespective of LVEF.

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

AIMS: Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise. METHODS AND RESULTS: We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO2 ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO2 in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden. CONCLUSION: Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.

Cardiometabolic Phenotyping in Heart Failure: Differences between Patients with Reduced vs. Preserved Ejection Fraction.

AIMS: We explored multiple cardiometabolic patterns, including inflammatory and congestive pathways, in patients with heart failure (HF). METHODS AND RESULTS: We enrolled 270 HF patients with reduced (<50%, HFrEF; n = 96) and preserved (≥50%, HFpEF; n = 174) ejection fraction. In HFpEF, glycated hemoglobin (Hb1Ac) seemed to be relevant in its relationship with inflammation as Hb1Ac positively correlated with high-sensitivity C-reactive protein (hs-CRP; Spearman's rank correlation coefficient ρ = 0.180, p < 0.05). In HFrEF, we found a correlation between Hb1Ac and norepinephrine (ρ = 0.207, p < 0.05). In HFpEF, we found a positive correlation between Hb1Ac and congestion expressed as pulmonary B lines (ρ = 0.187, p < 0.05); the inverse correlation, although not significant, was found in HFrEF between Hb1Ac and N-terminal pro-B-type natriuretic peptide (ρ = 0.079) and between Hb1Ac and B lines (ρ = -0.051). In HFrEF, we found a positive correlation between E/e' ratio and Hb1Ac (ρ = 0.203, p < 0.05) and a negative correlation between tricuspid annular systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (sPAP) (TAPSE/sPAP ratio) (ρ = -0.205, p < 0.05) and Hb1Ac. In HFpEF, we found a negative correlation between TAPSE/sPAP ratio and uric acid (ρ = -0.216, p < 0.05). CONCLUSION: In HF patients, HFpEF and HFrEF phenotypes are characterized by different cardiometabolic indices related to distinct inflammatory and congestive pathways. Patients with HFpEF showed an important relationship between inflammatory and cardiometabolic parameters. Conversely, in HFrEF, there is a significant relationship between congestion and inflammation, while cardiometabolism appears not to influence inflammation, instead affecting sympathetic hyperactivation.

The incremental value of multi-organ assessment of congestion using ultrasound in outpatients with heart failure.

AIMS: We investigated the prevalence and clinical value of assessing multi-organ congestion by ultrasound in heart failure (HF) outpatients. METHODS AND RESULTS: Ultrasound congestion was defined as inferior vena cava of ≥21 mm, highest tertile of lung B-lines, or discontinuous renal venous flow. Associations with clinical characteristics and prognosis were explored. We enrolled 310 HF patients [median age: 77 years, median NT-proBNP: 1037 ng/L, 51% with a left ventricular ejection fraction (LVEF) <50%], and 101 patients without HF. There were no clinical signs of congestion in 224 (72%) patients with HF, of whom 95 (42%) had at least one sign of congestion by ultrasound (P < 0.0001). HF patients with ≥2 ultrasound signs were older, and had greater neurohormonal activation, lower urinary sodium concentration, and larger left atria despite similar LVEF. During a median follow-up of 13 (interquartile range: 6-15) months, 77 patients (19%) died or were hospitalized for HF. HF patients without ultrasound evidence of congestion had a similar outcome to patients without HF [reference; hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.86-1.35], while those with ≥2 ultrasound signs had the worst outcome (HR 26.7, 95% CI 12.4-63.6), even after adjusting for multiple clinical variables and NT-proBNP. Adding multi-organ assessment of congestion by ultrasound to a clinical model, including NT-proBNP, provided a net reclassification improvement of 28% (P = 0.03). CONCLUSION: Simultaneous assessment of pulmonary, venous, and kidney congestion by ultrasound is feasible, fast, and identifies a high prevalence of sub-clinical congestion associated with poor outcomes.

Impact of diabetes on cardiopulmonary function: the added value of a combined cardiopulmonary and echocardiography stress test.

Type 2 diabetes mellitus (T2DM) represents a major health issue worldwide, as patients with T2DM show an excess risk of death for cardiovascular causes, twice as high as the general population. Among the many complications of T2DM, heart failure (HF) deserves special consideration as one of the leading causes of morbidity and reduced life expectancy. T2DM has been associated with different phenotypes of HF, including HF with reduced and preserved ejection fraction. Cardiopulmonary exercise testing (CPET) can evaluate the metabolic and ventilatory alterations related to myocardial dysfunction and/or peripheral impairment, representing a unique tool for the clinician to study the whole HF spectrum. While CPET allows for a thorough evaluation of functional capacity, it cannot directly differentiate central and peripheral determinants of effort intolerance. Combining CPET with imaging techniques could provide even higher accuracy and further insights into the progression of the disease since signs of left ventricular systolic and diastolic dysfunction can be detected during exercise, even in asymptomatic diabetic individuals. This review aims to dissect the alterations in cardiopulmonary function characterising patients with T2DM and HF to improve patient risk stratification.

Arterial Hypertension and Cardiopulmonary Function: The Value of a Combined Cardiopulmonary and Echocardiography Stress Test.

Arterial hypertension (AH) is a global burden and the leading risk factor for mortality worldwide. Haemodynamic abnormalities, longstanding neurohormonal and inflammatory activation, which are commonly observed in patients with AH, promote cardiac structural remodeling ultimately leading to heart failure (HF) if blood pressure values remain uncontrolled. While several epidemiological studies have confirmed the strong link between AH and HF, the pathophysiological processes underlying this transition remain largely unclear. The combined cardiopulmonary-echocardiography stress test (CPET-ESE) represents a precious non-invasive aid to detect alterations in patients at the earliest stages of HF. The opportunity to study the response of the cardiovascular system to exercise, and to differentiate central from peripheral cardiovascular maladaptations, makes the CPET-ESE an ideal technique to gain insights into the mechanisms involved in the transition from AH to HF, by recognizing alterations that might be silent at rest but influence the response to exercise. Identifications of these subclinical alterations might allow for a better risk stratification in hypertensive patients, facilitating the recognition of those at higher risk of evolution towards established HF. This may also lead to the development of novel preventive strategies and help tailor medical treatment. The purpose of this review is to summarise the potential advantages of using CPET-ESE in the characterisation of hypertensive patients in the cardiovascular continuum.

Determinants of Adherence to the Mediterranean Diet: Findings from a Cross-Sectional Study in Women from Southern Italy.

The Mediterranean diet (MD)-the dietary pattern usually consumed by Mediterranean populations-can help promote a favorable health status and better quality of life. Uncovering the main factors associated with the adherence to MD may be useful in understanding and counteracting the global shift toward a Western diet, which has been documented also in the Mediterranean region. Here, we evaluated the adherence to MD and its major social and behavioral determinants in women from Catania, Southern Italy. This cross-sectional study included 841 women, aged 25-64 years, with no history of severe diseases. Adherence to MD was assessed by the Food Frequency Questionnaire and Mediterranean Diet Score (MDS). Associations between variables were tested by multivariable logistic regression analysis and expressed as an odds ratio (OR) with a 95% confidence interval (CI). Among social factors, medium and high educational levels were associated with an ideal intake of alcohol (OR = 4.059; 95%CI = 1.311-12.570; p = 0.015; OR = 4.258 95%CI = 1.068-16.976; p = 0.040; respectively), living in a couple with ideal intake of cereals (OR = 2.801 95%CI = 1.188-6.602; p = 0.018), and having children with an ideal intake of fruits (OR = 3.149; 95%CI = 1.245-7.762; p = 0.015). With respect to behaviors, current smoking was negatively associated with an ideal intake of meat (OR = 0.449; 95%CI = 0.0220-0.917; p = 0.028), while more engagement in physical activity was associated with an ideal intake of vegetables (OR = 6.148; 95%CI = 1.506-25.104; p = 0.011) and legumes (OR = 5.832; 95%CI = 1.414-24.063; p = 0.015). In line with these findings, moderately or highly physically active women were more likely to show medium or high adherence to MD than those who performed less physical activity (OR = 6.024; 95%CI = 1.192-30.440; p = 0.040; OR = 9.965 95%CI = 1.683-58.993; p = 0.011; respectively). Our results confirm an urgent need for public health strategies, which should take into account determinants of diet quality. Particularly, our study indicates that more engagement in physical activity is a major positive determinant of the adherence to MD.

Sclerostin is a possible candidate marker of arterial stiffness: Results from a cohort study in Catania.

Osteoporosis and cardiovascular disease are worldwide public health issues. Recent evidence indicates a possible role of the canonical Wnt/ß-catenin signalling pathway as a common mediator between these two diseases. The aim of the present study was to investigate the relationship between serum concentrations of sclerostin and Dkk1, two extracellular inhibitors of Wnt/ß-catenin signalling, with carotid intima-media thickness (CIMT) and with arterial stiffness, evaluated by measuring the pulse wave velocity (PWV) in an ambulatory population of adults. To this aim, 67 subjects were recruited in the 'Atherosclerosis and osteoporosis: identification of common pathogenetic factors' investigation. Serum sclerostin levels correlated positively with CIMT (r=0.314, p=0.03) and inversely with the augmentation index, a marker of arterial stiffness (r=-0.286, p<0.05), whereas Dkk1 did not. Moreover, in a multivariate linear regression model, sclerostin [ß -0.1472; p=0.0023; standard error (SE)=0.04620] was an independent predictor of PWV in the study subjects. Our study shows that, following adjustment for confounders, sclerostin is an independent predictor of arterial stiffness in an ambulatory population, whereas Dkk1 is not.

Deep vein thrombosis related to environment (Review).

The first-time venous thromboembolism (VTE) is less frequent than other thrombotic events, however, both the pulmonary embolism (PE) and the deep vein thrombosis (DVT) show a frequent morbidity. Many factors play as risk situations in determining VTE, and the air exposure to the fine and ultrafine particulate matter (PM) as PM10, PM2.5, PM0.1 is considered. Epidemiological studies have supported this association although both the effective burden of the association and the mechanisms are to date unclear. The PM concentrations and the exposure time are notable as emerging factors. Interestingly, the seasonal climate variations resulted as effective risk factor for appearance of VTE or DVT. There is a need to ameliorate the environment by reducing the air pollution at global scale.

Transition and heavy metals compared to oxidative parameter balance in patients with deep vein thrombosis: A case-control study.

Our study compared copper (Cu), zinc (Zn) and manganese (Mn), crucial for human normal physio-logy maintenance, and lead (Pb) levels as environmental pollutant, in subjects suffering of deep vein thrombosis of lower limbs (DVTs) vs. healthy subjects. Furthermore, we evaluated oxidative stress parameters, the thiobarbituric acid reactive substances (TBARS) as the sum of malondialdehyde or 1,1,3,3-tetraethoxypropane (MDA) and 4-hydroxynonenal 4-HNE) and cytosolic superoxide dismutase (Cu/Zn-SOD) concentrations in both groups. We recruited 24 DVT cases and 46 healthy subjects as controls. Questionnaire with socio­demographic, habits and lifestyle were collected. Hair concentrations of Zn, Mn, Cu and Pb were measured by ICP-MS, plasma concentrations of MDA and 4-HNE were measured by HPLC and SOD plasma concentrations were detected by ELISA test. A quantitative and qualitative variables comparison between cases and controls group was made by Mann-Whitney U test and Pearson's Chi-square test, respectively. We found low concentrations of Zn, Mn and Cu vs. high Pb concentrations in DVTs subjects. TBARS were found higher in the cases group, conversely, SOD concentrations were found lower in cases with respect to controls. Furthermore, we found the diet of pathological subjects significantly deficient in vegetables. These results are indicative of a lower enzymatic activity in patients, related to low transition metal levels in the DVTs and high levels of Pb, coupled with an unbalanced diet.

A systematic review of arterial stiffness, wave reflection and air pollution.

Arterial stiffening is associated with increased cardiovascular risk. Whether exposure to relatively high levels of air pollution is associated with arterial stiffening is unclear. We aimed to assess the association between exposure to major air pollutants and arterial stiffening. PubMed, SCOPUS and Web of Science databases (through 31 January 2017) were searched using a combination of terms related to exposure to gaseous [nitrogen dioxide (NO2), nitrogen oxides (NOx) and sulphur dioxide (SO2)] or particulate matter pollutants (PM2.5, PM10 and PM10-2.5), arterial stiffness (pulse wave velocity) and reflected waves (augmentation index, augmentation pressure). Pertinent information were extracted from selected studies. In this systematic review were included 8 studies with available data on air pollution and arterial stiffness/reflected waves parameters (8 studies explored the effects of exposure to particulate matter pollutants, 3 studies the effects of exposure to gaseous pollutants); seven of them reported increased arterial stiffness/reflected waves after exposure to air pollution (6 of 8 studies after particulate matter pollutants; 2 of 3 studies after gaseous pollutants). Arterial stiffness and reflected waves were increased in the majority of the studies after both short- and long-term exposure to air pollutants. In conclusion, available evidence supports an association of main air pollutants with increased arterial stiffness and reflected waves. This finding may have implications for population-based strategies for the reduction of arterial stiffness, a vascular biomarker and an intermediate endpoint for cardiovascular disease.

Plasma heme oxygenase-1 is decreased in peripheral artery disease patients.

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. A number of emerging risk factors, including oxidative stress biomarkers, free radicals and heat shock proteins, may add to the established risk factors for cardiovascular disease (CVD). The present study assessed surrogate markers of oxidative stress, including total reduced glutathione (GSH), lipid hydroperoxides (LOOH), isoprostanes, heme oxygenase­1 (HO­1) and metabolic biomarkers, such as adiponectin and lactate, in PAD patients (n=27). Healthy age­matched volunteers (n=27) served as controls. GSH and LOOH were evaluated by measuring total thiol groups and iron oxidation, respectively, by spectrophotometric analysis. Adiponectin, isoprostanes and HO­1 levels were determined using commercially available ELISA kits and lactate level was determined colorimetrically. Results from patients with PAD demonstrated no significant difference in GSH content and LOOH formation when compared with healthy controls (5.1±7.6 vs. 6.9±9.1 nmol/ml and 6.8±14.2 vs. 8.3±14.9 nmol/ml, respectively), however, isoprostanes were demonstrated to be significantly reduced (3.8±4.8 pg/ml vs. 120±91 pg/mll; P<0.001). Furthermore, HO­1, a protective heat shock protein, was significantly reduced in PAD patients (0.8±0.7 vs. 3.4±1.3 ng/ml; P<0.001). Adiponectin, an antiatherogenic adipokine, was not significantly different between the two groups (1.4±0.2 vs. 1.5±0.5 µg/ml), whereas serum lactate was significantly higher in PAD patients compared with controls (0.11±0.01 vs. 0.1±0.01 mM; P<0.05). Using multivariate analysis, HO­1, hypertension, smoking and dyslipidemia were indicated to be independently associated with the presence of PAD, while only ankle­brachial index was an independent predictor of severity of PAD. The oxidative pathway may be partially involved in the onset and progression of PAD and may represent a target to reduce the risk of ischemic events.

Low levels of inflammation and the absence of subclinical atherosclerosis in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Patients with RA have an increased risk for the development of cardiovascular diseases, however, the pathophysiological mechanisms of arterial complications in RA remain to be fully elucidated. Understanding the early markers of vascular damage may aid in preventing cardiovascular complications in patients with RA. The current study investigated this by recruiting 30 patients with RA and 30 healthy subjects. Intima­media thickness (IMT) was used to detect the presence of atherosclerotic disease and was measured in the carotid and femoral arteries. Tumor necrosis factor α, interleukin­6 (IL­6), IL­8, IL­10 and matrix metalloproteinase­2 were measured as markers of inflammation. An IMT ≥0.9 mm was observed in 7/30 patients with RA, however, no significant differences between patients with RA and the controls were observed in the inflammatory markers analyzed. Of note, these results indicated that the appropriate management of RA may have affected the inflammatory status of these patients and consequently may have impacted upon subclinical atherosclerosis.

Circulating miR-130a, miR-27b, and miR-210 in Patients With Peripheral Artery Disease and Their Potential Relationship With Oxidative Stress.

Some emerging risk factors such as oxidative stress biomarkers and microRNAs (miRs) may add additional value to the established risk factors for peripheral artery disease (PAD). We enrolled 27 patients with PAD and 27 age-matched controls. We examined the levels of a series of miRs (miR-130a, miR-27b, and miR-210) in serum samples. The level of well-established oxidative stress biomarkers, such as lipid hydroperoxides, isoprostanes, hemeoxygenase-1 (HO-1) and reduced glutathione, was also measured in plasma and their relationship with the miRs was determined. Levels of miR-130a, miR-27b, and miR-210 were significantly increased in patients with PAD when compared to the controls. The level of miR-130 was positively correlated with body mass index, whereas miR-210 was inversely associated with pain-free walking distance (PfWD). None of the evaluated miRs was associated with lowered PfWD of patients with PAD (stage IIa > 250 m, IIb < 250 m) or oxidative stress parameters. In conclusion, our findings suggest the need for more research to assess if miRs can serve as useful markers for the early diagnosis and monitoring of PAD.

Plasma Levels of Inflammatory Biomarkers in Peripheral Arterial Disease: Results of a Cohort Study.

Previous research analyzed the level of plasma inflammatory markers in patients with coronary disease, but very few studies have evaluated these markers in patients with peripheral arterial disease (PAD). The objective of this study was to investigate the plasma levels of inflammatory markers in patients with PAD and in healthy controls. The following plasma levels of biomarkers were measured in 80 patients with PAD (mean age 68 ± 5 years) and in 72 healthy participants (mean age 67 ± 6 years): interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), L-selectin (LS), neopterin (N), P-selectin (PS), E-selectin (ES), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and matrix metalloproteinase 2 (MMP-2), and 9 (MMP-9). Significantly higher levels of IL-6 (P < .001), TNF-α (P < .0001), ES (P < .0001), LS (P < .0001), PS (P < .0001), ICAM-1 (P < .001), VCAM-1 (P < .001), N (P < .001), MMP-2 (P < .001), and MMP-9 (P < .005) were found in the patients with PAD. Patients with PAD show a inflammation marker profile different from that of control participants. Reducing the high plasma levels of inflammatory markers could be a new therapeutic approach both for the prevention and the treatment of PAD.

Arterial Plaques in Peripheral Arteries Diagnosed by Ultrasound in a Cohort of Patients With Type 2 Diabetes Mellitus: A Single-Center Surveillance.

Macroangiopathy (eg, peripheral arterial disease) diagnosis in type 2 diabetes mellitus (T2DM) can be carried out by ultrasound. A surveillance study was performed in 366 consecutive patients (166 patients with T2DM and 200 non-T2DM) aiming to evaluate the frequency of single or multiple arterial plaques (Aplqs) in lower limbs and the relationship with different factors (age, duration of T2DM, glycemic balance, DM treatment, smoking habit, and microalbuminuria). Single and multiple Aplqs, respectively, were found in 10.2% and 38.6% among the patients with T2DM. Age, male gender (P < .0002), duration of T2DM (P < .009), insulin therapy (P < .03), and mediocalcinosis (P < .001) were risk factors in patients with T2DM. In conclusion, Aplqs of lower limbs are frequent in T2DM and several factors can play a determining role. Ultrasound is a helpful diagnostic tool.

Familial 1q22 microduplication associated with psychiatric disorders, intellectual disability and late-onset autoimmune inflammatory response.

BACKGROUND: Despite the extensive use of chromosomal microarray technologies in patients with neurodevelopmental disorders has permitted the identification of an increasing number of causative submicroscopic rearrangements throughout the genome, constitutional duplications involving chromosome 1q22 have seldom been described in those patients. RESULTS: We report on a pedigree with seven affected members showing varying degrees of behavioural and emotional disturbances including general anxiety disorder, mood disorders, and intellectual disability. Two adult female patients also showed late onset autoimmune inflammatory responses characterized by alopecia, skin ulcers secondary to inflammatory vasculitis, interstitial lung disease, and Raynaud's phenomenon. Array-CGH analysis identified in the affected individuals a 290 Kb microduplication in the chromosome 1q22. The rearrangement involves eleven known genes and is not present in the databases of polymorphic copy number variants. CONCLUSIONS: The rearrangement segregates with the neurological clinical features observed in our patients, suggesting that dosage imbalance of one or more genes in this genomic region may lead to the observed phenotype. The association between the microduplication and the inflammatory disease is much less evident. Additional reported patients carrying similar microduplications are needed to clarify this aspect.