Increased Carotid Intima-media Thickness Research Articles

Abnormally increased carotid intima media-thickness and elasticity in patients with Morquio A disease

BackgroundCardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities.MethodsProspective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values.ResultsMorquio A patients demonstrated significantly higher (P < 0.001) adjusted carotid intima-media thickness (cIMT), mean (SD) of 0.56 mm (0.03) compared to control subjects, 0.44 mm (0.04). The Morquio A cohort had significantly greater adjusted carotid elasticity (carotid cross-sectional compliance + 43%, P < 0.001; carotid incremental elastic modulus − 33%, P = 0.003) than control subjects and other MPS patients. Aortic root dilatation was noted in 56% of the Morquio A cohort, which also had highly prevalent mitral (73%) and aortic (82%) valve thickening, though hemodynamically significant valve dysfunction was less frequent (9%).ConclusionsIncreased carotid elasticity in Morquio A patients is an unexpected contrast to the reduced elasticity observed in other MPS. These Morquio A cIMT findings corroborate MPS IVA arterial post-mortem reports and are consistent with cIMT of other MPS. Aortic root dilatation in Morquio A indicates arterial elastin dysfunction, but their carotid hyperelasticity indicates other vascular intima/media components, such as proteoglycans, may also influence artery function. Studying MPS I and IVA model systems may uniquely illuminate the function of glycosaminoglycan-bearing proteoglycans in arterial health.

Risk factors for calcification of the vertebrobasilar arteries in cardiovascular patients referred for a head CT, the SMART study

Background and purposeVertebrobasilar artery calcification (VBAC) has been associated with increased stroke occurrence. Little is known on VBAC risk factors, especially for patients with cardiovascular disease. We aimed to assess risk factors associated with VBAC in a cohort of cardiovascular patients referred for a head computed tomography (CT) scan. Materials and methodsAll patients who underwent a clinically indicated, unenhanced, thin slice head CT 6 months before or after inclusion in the SMART study were included. CTs were assessed for presence of VBAC (dichotomously). Relative risks of the associations of age, sex, diabetes mellitus (DM), obesity, body mass index, estimated glomerular filtration rate, hypertension, hyperlipidemia, use of lipid lowering medication, smoking status, high sensitivity C-reactive protein, ankle-brachial index (ABI; ≤0.90, ≥1.30, continuous), internal carotid artery stenosis ≥70%, and carotid intima-media thickness (IMT) with VBAC were estimated using Poisson regression analysis with robust standard errors, adjusted for age and sex. ResultsOf the 471 patients included (57% male, median age 58 [interquartile range 47–63]), 117 (24.8%) showed VBAC. Presence of VBAC was associated with older age (RR per 10 years=1.70 [95%CI 1.46–1.99]), DM (RR=1.45 [95%CI 1.03–2.06]), obesity (RR=1.53 [95%CI 1.10–2.12]), ABI ≤0.90 (RR=1.57 [95%CI 1.02–2.41]), and an increased carotid IMT (RR=2.60 per mm [95%CI 1.20–5.62]). Other measurements were not associated with VBAC. ConclusionsWe identified several markers associated with VBAC in patients with cardiovascular disease referred for a head CT. Future investigation into the relationship between VBAC and stroke is warranted to determine the potential of VBAC in stroke prevention.

Abstract 34: Association of Carotid Intima-Media Thickness and Other Carotid Ultrasound Features With Incident Dementia in The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Background: Increased carotid intima-media thickness (cIMT), a measure of carotid artery thickness, and carotid plaque are predictors of cardiovascular disease and atherosclerosis. Likewise, increased interadventitial diameter (IAD), which references arterial remodeling, and lower carotid distensibility coefficient (DC), which indicates carotid stiffness, are also predictors. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer’s disease and related dementias. Therefore, we assessed the relationship of carotid measures and distensibility with incident dementia in the Atherosclerosis Risk in Communities (ARIC) study. Methods: 12,459 ARIC participants who had carotid ultrasound measurements in 1990-92 were followed through 2017 for incident dementia. Dementia cases were identified using in-person and phone cognitive status and informant assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazards ratios for incident dementia per 1-SD and per quintile increment in arterial index (cIMT, IAD, and DC) and for presence of carotid plaque. Results: Participants were aged 57±6 at baseline, 57% were female, and 23% were black. Over a median follow-up of 24 years, 2,224 dementia events were ascertained. After multivariable adjustments, the highest quintile of both cIMT and IAD in midlife were associated with increased risk of incident dementia (Table; HRs [95% CIs]: 1.33 [1.15, 1.54]; 1.24 [1.06, 1.46]), while presence of carotid plaque was not (HR [95% CI]: 1.06 [0.97, 1.15]). Additionally, higher distensibility was associated with lower risk of dementia (HR [95% CI] highest vs. lowest quintile: 0.73 [0.61, 0.88]). Conclusion: Increased cIMT, IAD, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.

Subclinical atherosclerosis is associated with incident atrial fibrillation: a systematic review and meta-analysis.

Coronary artery disease is an established risk factor for incident atrial fibrillation (AF), but it is unclear whether subclinical atherosclerosis also increases the risk of incident AF. Therefore, the aim was to assess the association between subclinical atherosclerosis, defined by increased carotid intima-media thickness (cIMT) or coronary artery calcium score (CACS), and incident AF. A systematic review of MEDLINE, EMBASE, and Cochrane was done to find all cohort studies investigating the association between subclinical atherosclerosis, defined by increased cIMT or CACS, and incident AF. Eligible articles had to be available in an English full-text version; include adults over the age of 18 years; include ≥100 participants; and have a follow-up period ≥12 months. Data on cIMT were pooled using a fixed-effects model, while data on CACS (I2 >25) were pooled using a random-effects model. Five studies on cIMT including 36333 patients and two studies on CACS including 34603 patients were identified. All studies investigating the association between increased cIMT and incident AF showed a significant association, with an overall hazard ratio (HR) of 1.43 [95% confidence interval (CI) 1.27-1.59]. The two studies investigating the association between increased CACS and AF also showed a significant association with an overall HR of 1.07 (95% CI 1.02-1.12). Data from seven observational studies suggest that subclinical atherosclerosis defined by increased cIMT or CACS is associated with an increased risk of incident AF. These findings emphasize the need for further research investigating whether treatment of subclinical atherosclerosis should be a part of the initiatives to prevent AF.

Elevated 1-h post-load plasma glucose levels in normal glucose tolerance children with obesity is associated with early carotid atherosclerosis

ContextEvidence suggests that the 1-h post-load plasma glucose (1-h PG) ≥155mg/dL during an oral glucose tolerance test (OGTT) predicts development of type 2 diabetes (T2DM) and associated complications, among adults with normal glucose tolerance (NGT), but relevant data on children is scarce. ObjectivesTo investigate whether NGT children with obesity whose 1-h PG is ≥155mg/dL have an increased carotid intima-media thickness (IMT) and exhibit non-alcoholic fatty liver disease (NAFLD) diagnosed by ultrasonography, as compared with NGT subjects with 1-h PG <155mg/dL and impaired glucose tolerance (IGT). MethodsCardio-metabolic profile, OGTT, measurements of carotid IMT and liver ultrasonography were analyzed in 171 non-diabetic children with obesity. Subjects were divided into 3 groups: NGT subjects with a 1-h PG <155mg/dL, NGT subjects with a 1-h PG ≥155mg/dL, and IGT subjects. ResultsAs compared with NGT individuals with a 1-h PG <155mg/dL, NGT individuals with a 1-h PG ≥155mg/dL exhibited higher carotid IMT (0.75±0.15mm vs. 0.68±0.15mm; p<0.05). No significant differences were observed in carotid IMT between IGT and NGT subjects with a 1-h PG ≥155mg/dL (0.75±0.18mm vs 0.75±0.15mm; p>0.05). Of the three glycemic parameters, 1-h and 2-h PG, but not fasting glucose, were significantly correlated with carotid IMT. There were no significant differences for increased risk of having NAFLD between the three groups. ConclusionsThese data suggest that a value of 1-h PG ≥155mg/dL in children and adolescents with obesity is as important as IGT with respect to cardiovascular risks.

Associations of Arterial Stiffness and Carotid Atherosclerosis with Cerebral Small Vessel Disease in a Rural Community-Based Population.

Aims: We aimed to examine the associations of four extracranial artery indicators with cerebral small vessel disease (CSVD) and its total burden.Methods: A total of 904 individuals aged 55–65 years old were included from the Taizhou Imaging Study. CSVD markers, including lacunes (LAC), white matter hyperintensities (WMH), cerebral microbleeds (CMB), and perivascular spaces (PVS), were rated based on brain magnetic resonance imaging. We also measured extracranial artery indices, including the brachial-ankle pulse wave velocity (baPWV), the ankle-brachial index, the carotid intima-media thickness (IMT), and carotid plaque. Linear and binary logistic regressions were adopted to test the associations among these four artery indicators and each CSVD marker when appropriate. Additionally, ordinal and multinomial logistic regressions were performed to assess the relationships between artery indicators and total CSVD score (range from 0–4 points).Results: A total of 443 (49.0%) participants were found to have at least one of the CSVD markers, including 172 (19.0%) with WMH, 184 (20.4%) with LAC, 147 (16.3%) with CMB, and 226 (25.0%) with PVS. Increased baPWV was significantly associated with each CSVD marker, increasing carotid IMT was associated with LAC and PVS, and the presence of carotid plaque was associated with WMH volume and PVS. Moreover, per SD increment of baPWV (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.11–1.50) and the presence of carotid plaque (OR: 1.42, 95% CI: 1.05–1.92) were significantly associated with greater total CSVD scores.Conclusion: Increased baPWV and the presence of carotid plaque appear to be associated with total CSVD burden in rural regions in China.

Abstract TP204: Intima-Media Thickness in the Carotid Bifurcation, But Not Cardio-Ankle Vascular Index or Ankle-Brachial Index, is Related to Silent Brain Infarct on Magnetic Resonance Imaging in Healthy, Middle-Aged Japanese Individuals

Background: Carotid ultrasonography is currently the principal noninvasive tool for evaluating subclinical atherosclerosis and carotid artery disease. Increased carotid intima-media thickness (IMT) may precede the development of atherosclerotic plaques. Several studies have shown that increased IMT is associated with increased incidence of stroke. Silent brain infarct (SBI) has been proposed as a strong subclinical risk marker for future symptomatic stroke onset. However, the relationship between SBI and elevated IMT in healthy, middle-aged Japanese individuals has not been adequately examined. Methods: We examined 280 Japanese adults (92 women; mean age, 52.9 ± 5 years) with no history of cardiocerebrovascular disease. We assessed all participants’ periventricular hyperintensities, deep subcortical white matter hyperintensities, SBI on magnetic resonance imaging, cardio-ankle vascular index (CAVI)/ankle-brachial index (ABI), and various vascular risk factors. In addition, we measured intima-media thickness at the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA). Results: Participants were categorized into two groups according to the presence or absence of SBIs, and we then compared the clinical characteristics of the two groups. Age, hypertension, increased HbA1c level, and decreased estimated glomerular filtration rate were found to be significantly associated with the SBI group. The odds ratio (OR) of the maximum IMT at the CB for the presence of SBI was 4.016 (95% confidence interval [CI], 1.565-10.304), even after adjusting for potential confounding factors. In contrast, the ORs of maximum IMT at the ICA and CCA as well as CAVI and ABI were not significant. Participants with IMTs ≥2 mm at the CB had a higher probability of the presence of SBI (OR, 26.451; 95% CI, 2.404-291.00). Conclusion: The maximum IMT at the CB was significantly correlated with the presence of SBI on MRI, but ABI or CAVI did not show significant correlation. Thus, compared to CAVI or ABI, carotid ultrasonography appears to be a very useful tool for noninvasively detecting SBI. In particular, IMTs ≥2 mm at the CB on carotid ultrasonography may be practical for identifying SBIs among middle-aged Japanese individuals.

Circulating de novo Donor Specific Antibodies and Carotid Intima-media Thickness in Pediatric Kidney Transplant Recipients, A Pilot Study.

Background: The presence of circulating de novo donor specific anti-HLA antibodies (dnDSA) has been implicated in an immune-mediated form of accelerated systemic arteriosclerosis in adult heart and kidney transplant recipients, however this has not been previously investigated in pediatric kidney transplant recipients. Carotid intima-media thickness (CIMT) is a reliable method for detection of arteriosclerosis. We hypothesized that children who develop dnDSA after kidney transplant would have increased CIMT compared with those who remain dnDSA negative.Methods: A prospective, controlled pilot cohort study of 38 transplant patients and 20 healthy controls was conducted to investigate the association between CIMT and development of dnDSA after kidney transplant. CIMT, anthropometrics, blood pressure and lipid panel were measured at 1, 18, and 30 months post-transplant. DSA was checked at 6, 12, 18, 24 and 30 months post-transplant. CIMT of DSA positive transplant recipients was compared to DSA negative and controls.Results: Of the 38 transplant recipients, 7 patients developed dnDSA by 18–30 months post-transplant. Among 5 dnDSA positive patients who did not receive treatment for DSA prior to CIMT measurement (n=6 observations), the median CIMT was 0.505 mm (95% CI 0.454–0.560 mm) at 18–30 months post-transplant, compared to 0.455 mm (95% CI 0.440–0.470) in DSA negative transplant recipients (n = 54 observations of 30 patients) and 0.450 mm (95% CI 0.436–0.460) in the healthy controls (20 observations of 20 patients). Presence of dnDSA was independently associated with a 7.8% increase in CIMT compared to those without dnDSA (p=0.006), after adjusting for race, hypertension, dyslipidemia, and abdominal obesity.Conclusions: Development of dnDSA was associated with increased CIMT, an indicator of arteriosclerosis, in a cohort of dnDSA positive pediatric kidney transplant recipients. The association between dnDSA and CIMT was independent of traditional CV risk factors, including hypertension, dyslipidemia, and abdominal obesity.

Relationship between heart rate variability and carotid intima-media thickness in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

Both increased carotid intima-media thickness (cIMT) and low heart rate variability (HRV) have been associated with cardiovascular mortality and morbidity. Thus, the aim of this study was to investigate whether cardio autonomic alterations are accompanied or not by subclinical atherosclerosis in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). cIMT measures and 5-min HRV analyses were performed in apparently healthy adults. Heart rate variability was evaluated by linear time and frequency domain analyses. cIMT was defined as the average between the mean left and mean right cIMT values and was analysed as continuous and categorized variables (P≥75 or P<75). Multiple linear models using continuous variables and multivariate logistic regression with categorized cIMT and HRV quartiles were performed. Out of 7256 participants eligible for analyses, 23·4% presented cIMT≥75th percentile. Heart rate variability variables were reduced in cIMT≥P75 in comparison with cIMT<P75: SDNN 33·0 versus 37·0ms, P<0·001; RMSSD 22·0 versus 26·0ms, P<0·001; LF 191·0 versus 260·0ms2 , P<0·001; HF 164·0 versus 238·5ms2 , P<0·001. In crude analysis, an increased odds ratio for cIMT≥P75 was verified within the lowest two quartiles of LF and HF, but significances did not remain after adjustments for anthropometric and clinical variables. Considering the entire sample, subjects with cIMT≥P75 presented lower HRV values, but no independent relationships were detected between cIMT and HRV after multivariate adjustment.

ENERGI, MAKRONUTRIEN, DAN CAROTID INTIMA-MEDIA THICKNESS (CIMT) PADA REMAJA OBESITAS [Energy, Macronutrients, and Carotid Intima-Media Thickness (CIMT) in Obese Adolescents]

Obesity prevalence is increasing in adolescents. Subclinical chronic infl ammation in obesity causes complication, such as atherosclerosis. Cardiovascular disease is one of the complications of obesity that causes premature death. Carotid intima-media thickness (CIMT) is a subclinical marker of atherosclerosis which easily performed and noninvasive. Early detection of atherosclerosis can improved outcome. Healthy diet have a negative correlation with CIMT meanwhile high calori diet increase CIMT. This study aimed to examine the eff ect of energy and macronutrients intake on CIMT in obese adolescents. A cross sectional study was conducted on 59 adolescents aged 13-16 years old with obesity in pediatric clinic of Dr. Soetomo General Hospital using consecutive sampling method. Dietary intake was obtained through 1 x 24 hours food recall. Anthropometric measurements include body height and weight. Body Mass Index (BMI) was calculated. Obesity is defi ned as BMI higher than 95th percentile based on age and gender (CDC 2000 curve). CIMT examination was performed using B mode ultrasonography on the neck. Statistical analysis was perfomed using mutiple linear regression to analyze the eff ect of total energy, fat, and carbohydrate on CIMT. There were 59 obese adolescents included in this study, consist of 27 (45.8%) female adolescents and 32 (54.2%) male adolescents. No eff ects of total energy, carbohydrate, and fat on CIMT was found in obese adolescents (p&gt;0.05). Further research with more subjects and at least 2x24 hours food recall are needed to assess the eff ect of calories and macronutrients on CIMT in obese adolescents.

B-mode ultrasound assessment of carotid intima–media thickness among adult diabetics and normal adults in Gombe, Northeastern Nigeria

Background: The carotid intima–media thickness (CIMT) has been established as an early predictor of general arteriosclerosis in patients with diabetes. However, there is a paucity of information on CIMT of the common carotid artery (CCA) in healthy patients and in patients with risk factors for cardiovascular diseases such as diabetics, hypertension, and obesity in our environment. The aim of this study was to compare the CIMT in adult patients with diabetes and normal subjects in our institution in Gombe, Northeastern Nigeria. Materials and Methods: This case–control study was conducted over a period of 8 months (from April 2015 to December 2015) at Federal Teaching Hospital, Gombe, on 105 adult diabetic patients and 105 normal adults aged 18 years and above. The CCA was scanned with a PHILIPS HD-9 ultrasound scanner equipped with Doppler facility using a 7.5 MHz linear transducer. Three measurements of the CIMT were obtained at 1 cm proximal to the right and left carotid bulbs and the mean value of the measurements was recorded. Results: The age range of the diabetics comprising 54% of males and 46% of females was 23–79 years, while the range of control group comprising of 53% of males and 47% of females was 18–68 years. The overall mean CIMT (MCIMT) was 0.97 ± 0.4 mm and 0.73 ± 0.1 mm for diabetics and nondiabetic subjects, respectively. MCIMT was significantly higher in diabetics compared to nondiabetic subjects (P = 0.000). In diabetics, overall MCIMT values were 0.96 ± 0.2 mm and 0.91 ± 0.2 mm on the right and left sides, respectively, with a statistically significant difference between the two sides (P = 0.000), while in the normal group, the overall MCIMT values on the right and left sides were 0.75 ± 0.1 mm and 0.73 ± 0.1 mm, respectively, with a statistically significant difference between the two sides (P = 0.021). Furthermore, CIMT correlated positively with age in both diabetic and control groups. Conclusion: This study has shown a statistically significant increase in CIMT in diabetics compared to nondiabetics and age shows a significant correlation with CIMT. Reference value for CIMT in nondiabetic subjects in Northeastern Nigeria has been obtained.

Soluble ST2 is associated with increased carotid intima-media thickness in patients with type 2 diabetes mellitus: A case-control study.

Soluble suppression of tumorigenicity 2 (sST2) is a free form of membrane-bound ST2, which is a member of the interleukin-1 receptor family. Previous research has shown that sST2 is associated with diabetes, but cardiovascular risk factors have not been established.To analyze the relationship between sST2 and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM).After screening, a total of 118 subjects with T2DM were divided into 2 groups according to the measurement of CIMT (normal CIMT (NCIMT), n = 58; abnormal CIMT (ACIMT), n = 60), and 60 healthy subjects (normal control (NC), n = 60) were recruited in this study. CIMT was measured by a color Doppler ultrasound, and sST2 and other metabolic parameters were measured as well.The median concentration of sST2 was elevated in the ACIMT group (31.30 ng/ml) compared with the NCIMT group (28.29 ng/ml, P < .01) and the NC group (20.15 ng/ml, P < .01). After adjustment for age and sex, log sST2 was strongly associated with smoking history (β = 0.197, 95% CI, 0.084–0.311, P < .01), FPG level (β = 0.302, 95% CI, 0.162–0.442, P < .01) and HbA1c level (β = 0.296, 95% CI, 0.165–0.426, P < .01) and negatively correlated with HDL level (β = −0.153, 95% CI, −0.259 to −0.046, P < .01). Furthermore, sST2 level was a risk factor for increased CIMT in patients with T2DM.Increased sST2 level not only was associated with indicators of glucose and lipid metabolism but also was a risk factor for increased CIMT in patients with T2DM. Thus, sST2 may be a potential novel marker to assess the progression of diabetic macrovascular complications.

Lymphocyte to monocyte ratio may predict increased carotid intima-media thickness in patients with subclinical hypothyroidism

Inflammation has an important role in the pathogenesis of atherosclerosis. Lymphocyte-to-monocyte ratio (LMR) is accepted as an indicator of inflammation. Our aim was to scrutinize the relationship between LMR and subclinical atherosclerosis (SubAth) measured by carotid intima-media thickness (CIMT) in subclinical hypothyroidism (SubHT). Newly identified 190 SubHT patients were prospectively included into the study. Blood samples were taken for measuring laboratory parameters. Then, CIMT was computed. Patients were seperated into 2 groups by their CIMT value (Group-1: ≤0.9 and Group-2: >0.9 mm), and then stratified into tertiles pursuant to LMR and thyroid-stimulating hormone (TSH) levels, respectively. 59 patients had an increased CIMT value (Group-2), and 131 patients had a normal CIMT value (Group-1). Group-2 had a lower LMR and a greater high-sensitivity C-reactive protein (hsCRP), CIMT and TSH than Group-1 (for all, p < 0.05). Patients in the lowest tertile of LMR had a higher hsCRP, TSH and CIMT than those in the highest tertile (for all, p < 0.05). LMR was negatively associated with hsCRP, CIMT and TSH (for all, p < 0.05). LMR and TSH were independent predictors of increased CIMT. Pre-ultrasonographic LMR, which is a simple and inexpensive inflammatory marker, may give additional predictive information to determine SubAth in SubHT.

Paraoxonase-1 enzyme activity in rheumatoid arthritis patients: association with carotid intima-media thickness?

Objectives The aim was to find the relationship of biochemical determinants of paraoxonase-1 (PON1) enzyme activity with carotid intima-media thickness (IMT) as a surrogate marker of atherosclerotic cardiovascular (CV) disease risk in patients with rheumatoid arthritis (RA). Background There is strong correlation between patients with RA and CV morbidity and mortality that cannot be explained by traditional risk factors alone. And this could be due to abnormal function of high-density lipoproteins (HDL). HDL promotes cholesterol efflux, as well as protects low-density lipoprotein (LDL) against oxidation, and this ability has been referred to as an 'anti-inflammatory' function because the lipid oxidation products derived from LDL are highly proinflammatory. PON1 is an HDL-associated enzyme that promotes antioxidant and anti-inflammatory properties of HDL by preventing the formation of oxidized LDL and inactivating oxidized phospholipids. Patients and methods The authors conducted a case–control study, including 30 RA patients and 20 controls, enrolled in Menoufia, Egypt. B-mode Doppler ultrasound imaging to measure carotid IMT, C-reactive protein (CRP), erythrocyte sedimentation rate, lipid profile, and PON1 activity were measured. Results RA patients tended to be more dyslipidemic as evidenced by decreased HDL and increased total cholesterol, tryglycerides (TGD), and LDL, which showed increased carotid IMT and decreased PON1 activity than the control group. Patients with carotid plaque tended to be more dyslipidemic and plasma PON1 activity tended to be lower than in patients without carotid plaque. A significant correlation between plasma PON1 activity and systemic inflammation as measured by the erythrocyte sedimentation rate and hsCRP level was noted. Conclusion Our data suggest that the lower the activity of PON1, the higher the atherosclerotic CV disease risk in RA patients, as assessed by the presence of carotid plaque. There is a significant correlation between plasma PON1 activity and systemic inflammation in RA patients. Higher hsCRP levels were associated with lower PON1 activity.

Determination of association between nonalcoholic fatty liver disease and carotid artery atherosclerosis among nondiabetic individuals.

Background:Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the infiltration of fat in the liver cells. High levels of fat in the liver associated with increased risk of diseases like diabetes, high blood pressure and kidney disease, high cholesterol, metabolic syndrome.Aim and Objective:To determine the association between NAFLD and carotid intima media thickness (CIMT) among nondiabetic individuals.Materials and Methods:A total of 90 in-patients and outpatients (45 NAFL subjects and 45 patients with the normal liver as controls) with NAFL on abdomen ultrasound scan from Bangalore Baptist Hospital were included in our study. All the participants were subjected to a doppler study for carotid intima thickness and a blood sample (4 ml) was collected from all the subjects.Results:In this study, there is an elevated level of BMI, weight, dyslipidemia in NAFLD compared with controls. The present study suggests that cardiovascular risk factors such as increased carotid intima-media thickness occur more frequently among NAFLD patients compared to healthy individuals.Conclusion:We can conclude that NAFL has a significant association with higher cardiovascular risk in terms of carotid intima-media thickness, dyslipidemia, and hypoalphalipidemia. Lifestyle changes include weight loss, dietary changes, reduction of sedentary habits and physical exercise are recommended in the NAFL disease subjects with higher BMI and weight.

Associations of subclinical atherosclerosis with nonalcoholic fatty liver disease and fibrosis assessed by non-invasive score.

Nonalcoholic fatty liver disease (NAFLD) has been considered as a risk factor of adverse cardiovascular prognosis, but the relationship between subclinical atherosclerosis and NAFLD remains controversial. We aimed to investigate the impact of subclinical atherosclerosis on incident NAFLD and liver fibrosis. We included 3433 subjects aged ≥40years and free of NAFLD. Brachial-ankle pulse wave velocity (ba-PWV) and carotid intima-media thickness (CIMT) were measured at baseline to assess subclinical atherosclerosis status. At follow-up visit, NAFLD was diagnosed by hepatic ultrasound and fibrosis was assessed by NAFLD fibrosis score (NFS), fibrosis-4 score (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI). A total of 654 (19.1%) subjects developed NAFLD during the follow-up period of 4.3years. In the multivariate logistic regression models, each standard deviation (SD) increment of ba-PWV was associated with 20% (95% confidence interval [CI] 1.07-1.33), 22% (95% CI 1.08-1.39), 17% (95% CI 1.04-1.32) and 37% (95% CI 1.07-1.75) higher risk of incident NAFLD, higher NFS, FIB-4 and APRI respectively. Compared with the lowest quartile of ba-PWV, the highest quartile ba-PWV had 63% (95% CI 1.20-2.22), 112% (95% CI 1.42-3.17), 86% (95% CI 1.28-2.69) and 201% (95% CI 1.29-7.04) higher risk of incident NAFLD, higher NFS, FIB-4 and APRI respectively. Besides, per SD increase of CIMT was associated with a 12% (95% CI 1.01-1.24) higher risk of incident NAFLD. Increased ba-PWV was independently associated with incident NAFLD and higher probability of fibrosis, whereas CIMT was associated with incident NAFLD but not with fibrosis.

Migraine without Aura and Subclinical Atherosclerosis in Young Females: Is Gut Microbiota to Blame?

Background and Objectives: Migraine with aura (MA) could be considered a risk factor for developing atherosclerosis and cardio-vascular events. However, less is known about the relation between migraine without aura (MWA) and atherosclerosis. Our study aimed to assess whether young female migraineurs, with alterations of gut microbiota could associate early atherosclerosis. Materials and Methods: We conducted an exploratory cross-sectional, pilot study concerning 105 consecutive young females having MWA, with recent normal brain scans, that were free of cardio-vascular risk factors, non-smokers, not on oral contraception, not pregnant, and without thyroid or parathyroid diseases, chronic organ failure, cancer, or on probiotic or antibiotic treatment. Consecutive to assessment of gut microbiota, patients were assigned to two groups: dysbiosis positive (n = 45) and dysbiosis negative (n = 60). All study participants underwent clinical examinations with an assessment of migraine severity, body mass index and carotid intima-media thickness (CIMT), as well as laboratory workups. Statistical analysis was performed using a chi-squared test (χ2), a two-tailed t-test and a nonparametric Spearman’s correlation test. Results: The dysbiosis positive migraineurs showed a significant increase in CIMT along with several anthropometrical, biological and clinical particularities. Significant positive correlations between dysbiosis and CIMT, glycosylated hemoglobin, migraine severity and duration, tumor necrosis factor-alpha, and body mass index were found. Conclusions: Young female migraineurs with significant alterations of gut microbiota experienced early signs of atherosclerosis and displayed severe migraine disability, as well as multiple biological and clinical particularities.

Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations

Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54-year-old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima-media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C-terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research.

Children With Metabolically Healthy Obesity: A Review.

Children with “metabolically healthy obesity” (MHO) are a distinct subgroup of youth with obesity, who are less prone to the clustering of cardiometabolic risk factors. Although this phenotype, frequently defined by the absence of metabolic syndrome components or insulin resistance, was first described during the early 1980s, a consensus-based definition of pediatric MHO was introduced only recently, in 2018. The purpose of this review was to concisely summarize current knowledge regarding the MHO phenomenon in youth. The prevalence of MHO in children varies from 3 to 87%, depending on the definition used and the parameters evaluated, as well as the ethnicity and the pubertal status of the sample. The most consistent predictors of MHO in youth include younger age, lower body mass index, lower waist circumference, and lower body fat measurements. Various hypotheses have been proposed to elucidate the underlying factors maintaining the favorable MHO phenotype. While preserved insulin sensitivity and lack of inflammation were previously considered to be the main etiological factors, the most recent findings have implicated adipokine levels, the number of inflammatory immune cells in the adipose tissue, and the reduction of visceral adiposity due to adipose tissue expandability. Physical activity and genetic factors also contribute to the MHO phenotype. Obesity constitutes a continuum-increased risk for cardiometabolic complications, which is less evident in children with MHO. However, some findings have highlighted the emergence of hepatic steatosis, increased carotid intima-media thickness and inflammatory biomarkers in the MHO group compared to peers without obesity. Screening should be directed at those more likely to develop clustering of cardiometabolic risk factors. Lifestyle modifications should include behavioral changes focusing on sleep duration, screen time, diet, physical activity, and tobacco smoke exposure. Weight loss has also been associated with the improvement of insulin sensitivity and inflammation. Further investigative efforts are needed in order to elucidate the mechanisms which protect against the clustering of cardiometabolic risk factors in pediatric obesity, to provide more efficient, targeted treatment approaches for children with obesity, and to identify the protective factors preserving the MHO profile, avoiding the crossover of MHO to the phenotype with metabolically unhealthy obesity.

INTIMA-MEDIA THICKNESS OF THE CAROTID ARTERIES IS AFFECTED BY PUBERTAL MATURATION IN HEALTHY ADOLESCENTS.

ABSTRACTObjective: To contribute to the assessment of normal parameters of carotid intima-media thickness (CIMT) in healthy adolescents.Methods: A cross-sectional study was conducted through clinical, laboratory and ultrasound evaluation in 61 healthy adolescents. The inclusion criteria consisted of being in good health. The exclusion criteria were: presence or history of any chronic disease; being obese or overweight according to the World Health Organization (WHO) established criterion; continuous use of medication; or presenting a febrile condition or requiring medication within 48-hours prior to assessment. The pubertal stages were evaluated using the Tanner criteria. The high-resolution B-mode ultrasound examinations were performed according to the recommendations of the Consensus Statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force.Results: Adolescents were 14±2.6 years old, 62.3% female, 19 (31%) at early puberty (Tanner II and III), and 38 (62%) at late puberty (Tanner IV and V). They presented normal clinical and laboratorial parameters. CIMT values were 0.46±0.04 to 0.55±0.04 mm on the right and 0.48±0.02 to 0.53±0.04 mm on the left, according to pubertal maturation. CIMT values increased significantly on the right and left sides, according to pubertal stage (p<0.001 and p=0.016), and maximum internal diameters of the common carotid artery (p<0.025 and p<0.003). It was higher in males compared to females.Conclusions: An increase in CIMT in the healthy adolescents group, according to both age, and the degree of pubertal maturation should be considered when evaluating adolescents in diagnostic procedures.