Search Results (69)

Background: Over the past decade, few echocardiographic investigations have assessed myocardial strain parameters in women with a history of hypertensive disorders of pregnancy (HDP), and their findings have been inconsistent. Moreover, no study has comprehensively evaluated deformation indices of all biventricular and biatrial chambers in women post-HDP. This study aimed to examine the structural and functional myocardial properties of all cardiac chambers in a cohort of women with prior HDP at six years after delivery. Methods: We analyzed a consecutive cohort of women with previous HDP and compared them with a control group of normotensive healthy women matched for age and body mass index (BMI). Both groups underwent standard transthoracic echocardiography (TTE) supplemented by a detailed speckle tracking echocardiography (STE) evaluation of biventricular and biatrial myocardial deformation, along with carotid ultrasound, at six years postpartum. The primary endpoint was subclinical myocardial dysfunction, defined by impaired left ventricular global longitudinal strain (LV-GLS < 20%), while the secondary endpoint was early carotid atherosclerosis, defined by common carotid artery intima-media thickness (CCA-IMT) ≥ 0.7 mm. Results: The study included 31 women with previous HDP (mean age 42.3 ± 5.9 years) and 30 matched controls without HDP history (mean age 40.8 ± 5.0 years). The average follow-up duration was 6.1 ± 1.3 years postpartum. Despite preserved and comparable systolic function on conventional TTE, most myocardial strain and strain rate measures in both ventricles and atria were significantly reduced in the HDP group compared to controls. Subclinical myocardial dysfunction was detected in 58.1% of women with prior HDP, and 67.7% exhibited increased CCA-IMT (≥0.7 mm). A history of pre-eclampsia (PE) was independently associated with subclinical myocardial dysfunction (HR 4.01, 95% CI 1.05–15.3, p = 0.03). Both third-trimester BMI (HR 1.21, 95% CI 1.07–1.38, p = 0.003) and PE (HR 6.38, 95% CI 1.50–27.2, p = 0.01) independently predicted early carotid atherosclerosis. Notably, a third-trimester BMI above 27 kg/m² showed optimal sensitivity and specificity for identifying the secondary outcome. Conclusions: A history of PE is independently associated with a higher risk of subclinical myocardial dysfunction and early carotid atherosclerosis at six years postpartum. Full article

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

Introduction: Tumour-associated antigens (TAA) have been implicated in cell adhesion and cancer metastasis formation, but also in inflammatory processes, such as rheumatoid arthritis (RA). There has been little information about the possible associations of TAAs with RA-related clinical and laboratory parameters, with impaired vascular pathophysiology in RA, as well as about the effects of antirheumatic drugs on TAA production. Therefore, we determined the effects of one-year tofacitinib treatment on TAA levels, as well as correlations of TAA levels with various RA-associated and vascular parameters. Patients and methods: Altogether, 26 RA patients received 5 mg bid or 10 mg bid tofacitinib treatment for 12 months. Ultrasound-based functional vascular assessments, such as common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV), were determined at various timepoints. Serum concentrations of TAAs, including carcinoembryonic antigen (CEA), CA15-3, CA19-9, CA125, CA72-4, human epididymis protein 4 (HE4) and tissue polypeptide antigen (TPA), as well as various cytokines (TNF-α, IL-6, IL-8, VEGF) and PECAM-1 were determined by flow cytometry using a bead-based multiplex assay (LEGENDplex). Results: As previously determined and published, one-year tofacitinib treatment effectively suppressed disease activity and inflammation. Serum CA15-3 and HE4 levels significantly decreased both after 6 and 12 months compared to baseline (p < 0.05). CA19-9 levels significantly increased both after 6 and 12 months, while CEA levels transiently increased after 6 months versus baseline (p < 0.05). CA125, CA72-4 and TPA levels did not change over time. In various regression analyses, TAA levels showed variable, significant, positive associations with the 28-joint disease activity score (DAS28), CRP, ESR, RF, IL-6, TNF-α, IL-8 and PECAM-1 (p < 0.05). In addition, TAAs variably correlated with ccIMT and cfPWV (p < 0.05). Moreover, one-year changes in TAA levels variably correlated with DAS28, RF and some cytokines (p < 0.05), as well as with changes in DAS28, HAQ, CRP, ESR, IL-6, VEGF and ccIMT from baseline to 12 months (p < 0.05). Conclusions: JAK inhibition might decrease the levels of some TAAs and increase those of others. TAA levels might be associated with RA-related and vascular biomarkers. These results suggest that TAAs might play a role in inflammatory processes and vascular pathology underlying RA. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) corresponds to the condition of increased hepatic fat levels, which is the leading cause of hepatic failure and carcinoma. It is also an independent risk factor for cardiovascular disease (CVD) and mortality. MASLD can be due to obesity with insulin resistance and/or genetic predisposition, i.e., polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene. PNPLA3 polymorphism has been associated with increased hepatic fat levels, fibrosis, cirrhosis, and hepatocellular carcinoma, while its association with CVD remains to be fully understood. The aim of the current study was to examine whether the vascular phenotype of patients with MASLD differed between carriers and noncarriers of the PNPLA3 polymorphism. Adult patients with MASLD underwent clinical assessment, PNPLA3 genotyping, arterial tonometry for aortic stiffness measurement, and ultrasound examination of carotid arteries. In total, 117 patients with MASLD and no fibrosis (median hepatic stiffness was 4.71 kPa) were recruited. Carriers of the PNPLA3 polymorphism were younger and exhibited higher levels of ALT and APRI, as compared to wild-type subjects. On the other hand, carriers of the PNPLA3 polymorphism had not only a better metabolic profile (i.e., lower glucose and glycated hemoglobin) but also lower blood pressure, carotid intima-media thickness (IMT), and cardiovascular risk. In addition, PNPLA3 polymorphism was negatively correlated with aortic stiffness, which is a marker of arteriolosclerosis and vascular ageing. Our data are consistent with previous observations that in case of genetically-driven MASLD, there is an inverse association with common predictors of CVD. Our data support the view that the main contributors to CVD risk in patients with MASLD remain conventional cardiometabolic risk factors (i.e., age, glucose) that are more likely to be found in metabolic syndrome-related MASLD rather than genetically-driven MASLD, at least in the first stages of the disease. Full article

Background: There is a large overlap in the risk profiles and pathophysiologies of coronary artery disease (CAD) and cerebrovascular macroangiopathy. Therefore, this study aimed to analyse whether findings in CAD examination by coronary angiography or cardio-computer tomography (cardio-CT) are predictive of cerebrovascular macroangiopathy. Methods: Our study was a prospective, bicentric, cross-sectional cohort study. A total of 191 patients without earlier CAD diagnosis who underwent a cardio-CT scan or coronary angiography for the screening of CAD during clinical routine were serially included. Two groups were formed based on the criterion of CAD (yes/no), and both were subsequently examined using sonography of the carotids. The CAD scores Syntax score I, Agatston equivalent score, and CAD-RADS score as well as AHA classification were determined. In cerebrovascular examinations, plaques and stenoses of the internal carotid artery (ICA) and the intima-media thickness (IMT) of the common carotid artery were analysed. Demographic and medical data such as the presence of arterial hypertension, diabetes mellitus, obesity, nicotine abuse, and dyslipidaemia were documented. The primary endpoint was the nominal association between CAD and ICA stenosis controlled for age and gender; secondary endpoints were correlations between ICA stenoses and CAD scores. Results: Of the 191 serially recruited patients (58% male, 65 ± 11 yrs.), 101 fulfilled CAD criteria; 90 did not. Of all patients, 137 had ICA plaques, and 11 thereof had an ICA stenosis ≥ 50%. No association was found between CAD and ICA stenosis (Wald = 0.24; p = 0.624). Accordingly, there was no association between IMT and Syntax score I (Wald = 0.38; p = 0.706), Agatston equivalent score (Wald = 0.89; p = 0.380), CAD-RADS score (Wald = 0.90; p = 0.377), or AHA classification (Wald = 0.21; p = 0.837). Common cardiovascular risk factors, i.e., arterial hypertension (Wald = 4.47; p = 0.034), diabetes mellitus (Wald = 7.61; p = 0.006), and nicotine abuse (Wald = 0.83; p = 0.028), were associated with newly diagnosed CAD but not with ICA plaques, stenosis, or increased IMT. Conclusions: In our cohort, newly diagnosed CAD was associated with typical risk factors. However, neither CAD nor these risk factors were associated with cerebrovascular disease. This suggests that in patients without prior CAD diagnosis, findings from CAD examinations might not be reliably predictive of cerebrovascular disease. Full article

Background: Carotid intima-media thickness (IMT) is a noninvasive surrogate marker of subclinical atherosclerosis and cardiovascular disease risk. This study explored IMT distribution across three carotid artery segments in a large cohort of healthy individuals and identified the key factors associated with increased IMT. Methods: This study utilized data from the Kangbuk Samsung Health Study, a cohort of South Korean adults aged ≥ 18 years who underwent comprehensive annual or biennial health examinations. The analysis included 86,351 healthy individuals, excluding those with known carotid disease. IMT was measured using high-resolution B-mode ultrasonography across the three segments: common carotid artery (CCA), carotid bulb, and internal carotid artery (ICA). An increased IMT was defined as a measurement of ≥1.5 mm in any segment. Multivariable linear regression analyses were conducted to identify independent predictors of increased IMT. Results: The study population had a mean age of 46.7 years and was predominantly male (69.7%). The prevalence of thickened IMT was the highest in the carotid bulb, followed by the ICA and CCA. IMT increased progressively with age and was higher in males across all segments, with the disparity becoming more pronounced after 65 years of age. The carotid bulb displayed the largest absolute IMT values, whereas the ICA exhibited a sharper age-related increment. Increased CCA IMT was strongly linked to hypertension (beta, 0.11; p < 0.001) and diabetes mellitus (beta, 0.12; p < 0.001). Both CCA and ICA IMT showed a weak but significant association with dyslipidemia (beta, 0.03; p < 0.001). Conclusions: The IMT distribution and its determinants vary across carotid segments. CCA is a robust marker of systemic vascular health, whereas the carotid bulb is the most sensitive marker for detecting early atherosclerotic changes. This study provides novel insights into segment-specific IMT patterns and their association with cardiovascular risk factors in a large, healthy Asian population. Full article

Background/Objective: Vascular abnormalities are the primary histological changes in individuals undergoing radiotherapy for nasopharyngeal carcinoma (NPC). We sought to validate the hypothesis that the duration post-radiotherapy is linked to the progression of carotid intima-media thickness (IMT) and further explored its connection with mortality. Methods: Twenty-nine NPC patients who underwent radiotherapy and seventeen healthy controls were examined by carotid ultrasound for measurement of IMT and carotid plaque score at the common carotid artery (CCA), carotid bifurcation, and internal carotid artery, with follow-ups more than 6 years. Results: Initially, there was no discernible difference in internal carotid IMT between NPC patients and normal controls. However, a noteworthy increase in carotid IMT was observed after 6 years of radiotherapy (p < 0.0001). The carotid plaque score in NPC patients significantly exceeded that of the control group after 6 years (p < 0.0001). Linear regression demonstrated a positive correlation between carotid IMT and the duration post-radiotherapy. Logistic regression suggested that age and carotid IMT were predictors of mortality in NPC patients. Conclusions: Our study substantiates the positive correlation between carotid IMT and the duration of follow-up after radiotherapy. It found an increase in carotid IMT and plaque formation six years after radiotherapy compared to the control group. An increased carotid IMT may be correlated to an increased mortality rate and needs to be explored in future studies. Consequently, we recommend regular follow-up carotid ultrasonography for NPC patients undergoing radiation therapy. Full article

Background/Objectives: No previous study has provided a comprehensive evaluation of all biventricular and biatrial myocardial strain parameters in women with previous gestational diabetes mellitus (pGDM). Accordingly, we aimed at investigating the structural and myocardial deformation properties of all cardiac chambers in a cohort of pGDM women at 4 years postpartum. Methods: A consecutive cohort of pGDM women was compared to a control group of healthy women with previous uncomplicated pregnancy, matched by age, ethnicity and gestational week, at 4 years postpartum. Both groups of women underwent transthoracic echocardiography (TTE) implemented with speckle-tracking echocardiography (STE) and subsequent carotid ultrasonography. The primary endpoint was subclinical myocardial dysfunction, defined as left-ventricular (LV) global longitudinal strain (GLS) < 20%, whereas the secondary endpoint was early carotid atherosclerosis, defined as common carotid artery (CCA) intima-media thickness (IMT) ≥ 0.7 mm. Results: A total of 32 pGDM women (39.1 ± 6.5 yrs) and 30 matched healthy controls (40.8 ± 5.0 yrs) were analyzed. Despite normal and similar systolic function on conventional TTE, all biventricular and biatrial strain parameters were significantly lower in pGDM women than controls. Mean follow-up period was 4.0 ± 1.9 yrs. During follow-up, 62.5% of pGDM women developed subclinical myocardial dysfunction, and 78.1% of them were diagnosed with early carotid atherosclerosis. Third-trimester BMI (OR 1.88, 95% CI 1.19–2.98) and third-trimester glycosylated hemoglobin (HbA1C) (OR 2.34, 95% CI 1.08–5.04) were independently associated with the primary endpoint. Third-trimester BMI and HbA1C also independently predicted the secondary endpoint. Third-trimester BMI > 27 kg/m² and HbA1C > 33 mmol/mol showed the best sensitivity and specificity for predicting both endpoints. Conclusions: Women with a previous history of GDM complicated by overweight/obesity and uncontrolled diabetes have a significantly increased risk of subclinical myocardial dysfunction and early carotid atherosclerosis at 4 years postpartum. Full article

Background/Objectives: The interrelationship of thyroid volume and function with features of cardiovascular dysfunction has already been investigated but some aspects remain unclear, especially in terms of subclinical cardiovascular dysfunction in euthyroid patients. Intima-media thickness (IMT) measurement in ultrasound B-mode imaging in different vascular beds (most frequently within the common carotid artery) is one of the most important tools for the detection of subclinical atherosclerosis in both clinical practice and research. This article aimed to present the results of our research on the association between the thyroid evaluation parameters and the IMT measured in both the carotid and femoral arteries in euthyroid patients aged 18 to 65 years taking into account the influence of diabetes, hypertension, and excess body mass. Methods: We performed a retrospective cross-sectional analysis of data from patients with no thyroid disease who during planned hospitalization underwent thyroid ultrasound, determination of biochemical parameters of thyroid function, and Doppler ultrasound of carotid, vertebral, and lower extremities arteries with IMT measurement. Data from 45 people (females: 57.8%) were analyzed. Results: No significant correlations were found between biochemical parameters of thyroid function and IMT parameters. Thyroid volume was found to be significantly correlated with all parameters of the IMT within the superficial femoral artery (R = 0.407, p = 0.007 for the mean IMT calculated from the left side and the right side) and with minimal IMT within the common femoral artery taken from the left side and the right side (R = 0.342, p = 0.025). Selected IMT parameters were shown to be significantly higher in patients with arterial hypertension, diabetes, obesity, or metabolic syndrome in comparison to patients without the mentioned comorbidities. Using multiple linear regression, it was confirmed that parameters related to thyroid status do not significantly affect the IMT value. A significant effect of diabetes and, to a lesser extent, hypertension on the IMT value was confirmed, especially in the femoral arteries. Conclusions: In the population of euthyroid patients, thyroid volume correlates significantly with some parameters of femoral IMT. No significant correlations were found between thyroid biochemical parameters and IMT in both carotid and femoral arteries. A significant influence of diabetes and hypertension on the IMT value was confirmed, especially in the femoral arteries. Full article

Background/Objectives: Studies in adults have demonstrated the essential role of microRNAs in developing hypertension and their effect on hypertension sequelae. In this preliminary study, we aimed to investigate the expression of five miRNA particles, miRNA-21, miRNA-27a, miRNA-27b, miRNA-133a, and miRNA-145, in school-aged children with primary hypertension and to examine their correlations with blood pressure and arterial and heart properties. Methods: In 22 hypertensive children (15.1 ± 1.9 years), we measured blood pressure parameters (office, central, and 24 h), the urinary albumin/creatinine ratio, and the pulse wave velocity (PWV) before and after one hour of aerobic exercise. The left ventricular mass index (LVMI) and common carotid artery intima–media thickness (cIMT) were also assessed. The relative miRNA expression was calculated using the 2^−ΔΔCt method with miRNA-16 as an endogenous control and the pre-exercise miRNA expression levels as the control (baseline). Results: We found a statistically significant decrease in both the office and 24 h ambulatory diastolic blood pressure after 1 h of exercise (82.2 ± 8.5 mm Hg versus 78.6 ± 8.8 mm Hg, p = 0.01 and 75.0 ± 8.3 mm Hg versus 73.0 ± 7.4 mm Hg, p = 0.02). The increase in miRNA-133a expression after exercise correlated positively with the LVMI. Furthermore, the rise in miRNA-145 expression after exercise correlated negatively with the systolic and diastolic office and 24 h blood pressure and with markers of arterial damage: 24 h PWV and cIMT. Conclusions: In conclusion, miRNA-133a may be a biomarker of left ventricular hypertrophy in children with elevated blood pressure. Additionally, changes in miRNA-145 expression induced by exercise might reduce the blood pressure after exercise and protect against arterial damage. Both miRNA-133a and miRNA-145 may be involved in epigenetic alterations in children affected by primary hypertension that may contribute to the exacerbation of HMOD. Full article

Background: Transgender men use exogenous androgen for male pattern virilization. Hysterectomy and bilateral salpingo-oophorectomy (HBSO) is performed to stop the endogenous estrogen secretion. Cardiovascular disease (CVD) risk has been shown to increase with long-term use of androgens and the removal of estrogen. We aimed to investigate the CVD risk in these individuals by measuring internal and common carotid artery intima–media thicknesses (CIMT). Methods: In this cohort study, data were collected from transgender men who had undergone HBSO and used androgens for at least two years (median treatment duration was 5 years in our research). Cisgender women in the same age range were selected as the control group. Demographics, vital signs, and hematological values of transgender patients and cisgender women subjects in the control group were noted. CVD markers were compared with sonographically measured CIMT values. Results: The mean age and body mass index (BMI) of the study group were 32.6 and 25.3, respectively. Weight, systolic–diastolic blood pressure, hemoglobin, hematocrit, low-density lipoprotein (LDL), serum triglyceride (TG), HbA1c levels, internal CIMT, and common CIMT values of the study group were higher, while the high-density lipoprotein (HDL) level was significantly lower compared the control group (p1 = 0.025, p2 = 0.010, p3 = 0.002, p4 = 0.001, p5 = 0.001, p6 = 0.012, p7 = 0.008, p8 = 0.007, p9 = 0.013, and p10 = 0.001). There was also an increase in the body weight, BMI, LDL, and TG levels of the study group after the testosterone treatment (p1 = 0.025, p2 = 0.019, p3 = 0.001, p4 = 0.001, and p5 = 0.001). Conclusions: We demonstrated that the use of testosterone therapy in transgender men is associated with higher CIMT values. While further investigation is needed to assess morbidity and mortality rates, we recommend that regular clinical and radiological examinations be performed in these individuals to accurately evaluate the risk of CVD. Full article

Background: Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. Results: Individuals with DSPN exhibited lower EDV in the CCA and ICA (p < 0.0001 and p = 0.002), higher PI and RI in both CCA and ICA (all p < 0.0001), and higher CPS (p = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all p < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. Conclusions: Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity. Full article

Pathological studies have demonstrated that the adventitial layer is markedly thickened in Takayasu (TAK) as compared to large vessel giant cell arteritis (LV-GCA). An ultrasound (US) examination of the arterial vessels allows the determination of intima media thickness (IMT) and of adventitial layer thickness (extra media thickness (EMT)). No previous study has evaluated if there are differences in EMT thickness between TAK and LV-GCA. In this cross-sectional retrospective study of stored ultrasound (US) imaging, we have compared common carotid artery (CCA) EMT and IMT in a series of consecutive TAK and LV-GCA patients. US examination CCA IMT and EMT were significantly higher in TAK as compared to LV-GCA. With ROC curve analysis, we have found that an EMT > 0.76 mm has high sensitivity and specificity for TAK CCA examination. The percentage of CCA at EMT > 0.76 mm and the total arterial wall thickening were significantly higher in TAK group examinations. EMT thickness correlated with disease duration and IMT in the TAK group, as well as with the IMT and ESR values in the LV-GCA group. Upon multivariate logistic regression analysis, factors independently associated with TAK CCA were EMT > 0.76 mm and age. No significant variation in IMT and EMT could be demonstrated in subsequent US CCA examinations. Full article

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)—the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease. Full article

Cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Natural autoantibodies (nAAb) are involved in innate immunity, as well as autoimmunity, inflammation, and atherosclerosis. There have not been any studies assessing the effects of biologics on nAAbs in RA and AS, also in relation to vascular pathophysiology. Fifty-three anti-TNF-treated RA and AS patients were included in a 12-month follow-up study. Anti-citrate synthase (CS) and anti-topoisomerase I fragment 4 (TOPO-F4) IgM and IgG levels were determined by ELISA. Ultrasonography was performed to assess brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV). Other variables were also evaluated at baseline and 6 and 12 months after treatment initiation. Anti-TNF therapy improved FMD in RA and PWV in AS and stabilized ccIMT. TNF inhibition increased anti-CS IgM and IgG, and possibly also anti-TOPO-F4 IgG levels. Various correlation analyses revealed that nAAbs might be independently involved in autoimmunity as well as changes in inflammation and vascular pathology over time in biologic-treated patients (p < 0.05). We also found associations between anti-TOPO-F4 IgG and anti-Hsp60 IgG (p < 0.05). Baseline nAAb levels or nAAb level changes might determine changes in CRP, disease activity, FMD, PWV, and ccIMT over time (p < 0.05). The interplay between arthritis and inflammatory atherosclerosis, as well as the effects of anti-TNF biologics on these pathologies, might independently involve nAAbs. Full article