Carotid Intimal Thickness Research Articles

Association of cardiovascular risk estimate with degree of atherosclerosis in patients with type 2 diabetes mellitus

Background: Type 2 diabetes mellitus is one of the leading causes for global public health crisis mainly affecting the Asian countries. Cardivascular disease (CVD) is one of the leading contributors to morbidity and mortality for type 2 diabetes mellitus patients. Assessment of the cardiovascular risk in asymptomatic patients and advising them for proper preventive measures will help to bring down the morbidity and mortality. In this study we aim to find the correlation of carotid intima thickness (CIMT) with different risk scores estimating 10 years risk of cardiovascular disease. Method: It is a cross sectional study involving type 2 diabetes mellitus patient of age between 20 years and 80 years, without having any previous history of cardiovascular disease, cerebrovascular accident, chronic kidney disease and connective tissue disorder. Detailed history and examination was done along with blood investigations like fasting lipid profile, HbA1c, fasting and post prandial blood glucose, blood urea and creatinine. All these data were used to estimate 10 years cardiovascular risk using different risk engines - United Kingdom Prospective Diabetes Study (UKPDS) risk engine, Framingham Risk Score (FRS), Q risk and Atherosclerotic cardio vascular disease (ASCVD). All the patients were subjected for measurement of carotid intima thickness (CIMT) by ultrasonography. Correlation coefficient was calculated using SPSS software version 18. Result: Total 59 patient (40 males and 19 females) were included in the study. Mean age, duration of diabetes, HbA1c and CIMT were 56.3 ± 10 years, 8.1 ± 6.9 years, 8.2 ± 1.2% and 0.8 ± 0.2 mm respectively. Age, duration of diabetes, HbA1c, total cholesterol, low density cholesterol and triglyceride had significant positive correlation with CIMT (P Conclusion: In the absence of South Asian specific risk estimate algorithm Q risk and UKPDS risk score can be used with caution. CIMT is well established indicator of atherosclerosis, hence it can be used to estimate cardiovascular risk and to advise preventive measures.

Anti-malarial Drugs Reduce Vascular Smooth Muscle Cell Proliferation via Activation of AMPK and Inhibition of Smad3 Signaling

ObjectiveThe aim of this study was to investigate the effects of 2 anti-malarial drugs, chloroquine (CQ) and hydroxychloroquine (HCQ), on inhibition of vascular smooth muscle cell (VSMC) proliferation both in vivo and in vitro via Adenosine monophosphate-activated protein kinase (AMPK) activation.MethodsProtein and mRNA levels were determined by western blot analysis and real-time reverse transcription-polymerase chain reaction in primary rat VSMCs treated with CQ and HCQ, respectively. Cell proliferation was measured by flow cytometry and cell counting. Mice carotid arteries were ligated and treated with CQ or HCQ every other day for 3 weeks. Pathological changes of carotid arteries were visualized by both microscopy and fluorescence microscopy.ResultsCQ and HCQ increase AMPK phosphorylation in VSMCs. Both CQ and HCQ decrease platelet-derived growth factor-induced VSMC proliferation and cell cycle progression in an AMPK-dependent manner. In addition, CQ and HCQ inhibit Smad3 phosphorylation and VSMC proliferation induced by transforming growth factor-β1. Moreover, CQ and HCQ diminished neointimal proliferation in a mouse model of carotid artery ligation-induced neointima formation.ConclusionThe results demonstrated that CQ and HCQ inhibit cell proliferation and cell cycle progression in VSMCs via the AMPK-dependent signaling pathway. Carotid artery ligation-induced intima thickness was reduced in mouse arteries treated with CQ or HCQ, suggesting a role for antimalarial drugs in treating atherosclerosis and restenosis.

Cardiovascular and Metabolic Health of 74 Children From Women Previously Diagnosed With Polycystic Ovary Syndrome in Comparison With a Population-Based Reference Cohort.

Women with polycystic ovary syndrome (PCOS) have compromised cardiovascular health profiles and an increased risk of pregnancy complications. In order to evaluate potential consequences, we aim to compare the cardiovascular and metabolic health of the children from women with PCOS with a population-based reference cohort. We included children from women with PCOS between the age of 2.5 to 4 years (n = 42) and 6 to 8 years (n = 32). The reference groups consisted of 168 (3-4 years old) and 130 children (7-8 years old). In an extensive cardiovascular screening program, we measured anthropometrics and blood pressure (all children), heart function and vascular rigidity (young children), metabolic laboratory assessment and carotid intima thickness (old age-group). Results showed that young PCOS offspring have a significantly lower diastolic blood pressure (β = 2.3 [95% confidence interval, CI: 0.5-4.0]) and higher aortic pulse pressure (β = -1.4 [95% CI: -2.5 to -0.2]), compared to the reference population. Furthermore, a higher left ventricle internal diameter but a lower tissue Doppler imaging of the right wall in systole compared to the reference group was found. Older offspring of women with PCOS presented with a significantly lower breast and abdominal circumference, but higher triglycerides (β = -0.1 [95% CI: -0.2 to -0.1]), LDL-cholesterol (β = -0.4 [95% CI: -0.6 to -0.1]), and higher carotid intima-media thickness (β = -31.7 [95% CI: -46.6 to -16.9]) compared to the reference group. In conclusion, we observe subtle but distinct cardiovascular and metabolic abnormalities already at an early age in PCOS offspring compared to a population-based reference group, despite a lower diastolic blood pressure, breast, and abdominal circumference. These preliminary findings require confirmation in independent data sets.

Cardiovascular and Metabolic Outcomes in Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis.

Individuals with congenital adrenal hyperplasia (CAH) require glucocorticoid therapy to replace cortisol and to control androgen excess. We sought to evaluate the effects of glucocorticoid therapy on cardiovascular and metabolic outcomes in individuals with CAH. We searched bibliographical databases through January 2016 for studies evaluating cardiovascular risk factors in individuals with CAH treated with glucocorticoids compared with controls without CAH. We used a random-effects model to synthesize quantitative data. We included 20 observational studies (14 longitudinal, six cross-sectional) with a moderate to high risk of bias. The average dose of glucocorticoids (in hydrocortisone equivalents) was 9 to 26.5 mg/m2/d. In the meta-analysis (416 patients), compared with controls without CAH, individuals with CAH had increased systolic blood pressure [weighted mean difference (WMD), 4.44 mm Hg; 95% CI, 3.26 to 5.63 mm Hg], diastolic blood pressure (WMD, 2.35 mm Hg; 95% CI, 0.49 to 4.20 mm Hg), homeostatic model assessment of insulin resistance (WMD, 0.49; 95% CI, 0.02 to 0.96), and carotid intima thickness (WMD, 0.08 mm; 95% CI, 0.01 to 0.15 mm). No statistically significant differences were noted in fasting blood glucose, insulin level, glucose, or insulin level after 2-hour glucose load or serum lipids. Data on cardiac events were sparse, and most of the literature focused on surrogate outcomes. Individuals with CAH demonstrate a high prevalence of cardiovascular and metabolic risk factors. The current evidence relies on surrogate outcomes. Long-term prospective studies are warranted to assess strategies for reducing cardiovascular risk in individuals with CAH.

Personal Exposure to PM2.5, Black Carbon and Carbon Monoxide and Their Effects on Atherosclerosis: A Cross Sectional Assessment in Bangladesh

About 40% of the world’s population are exposed to hazardous particles from biomass fuel use at households. Effects of such exposures on preclinical markers of cardiovascular diseases (CVD) are practically challenging to measure and mostly unexplored in low- and middle-income countries. GEOHealth study is examining the effect of individual level exposures to PM 2.5, black carbon (BC) and carbon monoxide (CO) on atherosclerosis among 600 biomass fuel users in rural Bangladesh.We are measuring PM 2.5 by gravimetric method using personal air samplers (RTI MicroPEM™). BC is being determined by reflectance measurement using an EEL-type smoke stain Reflectometer. CO is measured by Lasker EL-USB CO data logger. We assessed Carotid intima thickness (cIMT), a marker of atherosclerosis, using the SonoSite MicroMaxx ultrasound machine equipped with a L38e/10-5 MHz transducer. We are using the mean of the near and far walls of the maximum common carotid artery (CCA) IMT from both sides of the neck as the outcome variable. Structured questionnaire is used to record important co-variates.The primary analysis was conducted among 100 women (mean age 40±8 years), who has been using biomass fuel in traditional stoves for 20±9 years. They were all non-smoker with low (<5 µg/L) exposure to water arsenic and not known to have any CVD. Average 48 hour exposure to PM2.5, BC and CO was 124µg/m3 (SD 108), 4.8 µg/m3 (SD 2.1) and 1.2 ppm (SD 0.9) respectively. Mean cIMT is 740.9µm (SD 78). We will construct a multiple linear regression model and strength of association adjusted for important co-variates will be reported. We plan to complete data analysis on 200 samples by June 2018 and expect to present the finding at the ISEE meeting.Findings will help establish effects of HAP on atherosclerosis providing insights into magnitude, underlying mechanism and prevention strategies of the problem.

Neutrophils and neutrophil-lymphocyte ratio: Inflammatory markers associated with intimal-media thickness of atherosclerosis

IntroductionCardiac-cerebral vascular diseases (CCVDs) are global health problems due to the characteristic of high mortality. It is found that atherosclerosis (AS), a main cause of CCVDs, is significantly relevant to the change of intimal and media thickness. Neutrophil count (NEU) and neutrophil-lymphocyte ratio (N/L) are recognized possible risk factors for atherosclerosis (AS). However, there are few studies on the separate relationship between carotid intimal thickness, media thickness and NEU, N/L. This study explored the respective effects of NEU and N/L on AS and intimal, media thickness. Materials and methodsThe χ2, Spearman's rho test, and multiple linear regression were implemented to analyze the relevance between blood parameters and intimal-media thickness. The potential factors, affecting non-depression time (NDT), is identified by univariate Cox regression. ROC curve was performed to determine the ability of blood parameters to predict intimal-media thickness. Immunohistochemistry was implemented. Results and conclusionBased on χ2, Spearman's rho test and multiple linear regression, NEU is related with intimal thickness (P < 0.05). Furthermore, NEU can predict the intimal thickness through the ROC curve. What's more, N/L is a risk factor of carotid media thickness (P < 0.05) by the Spearman's rho test, and is also correlated with poor NDT (P < 0.05) based on univariate Cox proportional regression analysis. Through ROC curve, N/L can predict the carotid media thickness. The carotid atherosclerotic endarterium is richest in macrophagocytes, and the arrangement of endotheliocytes is disordered. In summary, the increased NEU and N/L respectively have a strong correlation and precise predictability for carotid intimal and media thickness of atherosclerosis.

Carotid Artery Intima Media Thickness in Predicting Coronary Artery Disease in Type II Diabetes Mellitus

Diabetes Mellitus is a chronic, common metabolic disorder characterised by high blood sugar levels over a prolonged period. Atherosclerosis involving the coronary, cerebral and peripheral (lower extremity) arteries is the predominant cause of diabetes related mortality, responsible for up to 70% of all deaths in patients with this disease. Coronary angiography (CAG) has been considered as the gold standard for the assessment of the degree of Coronary atherosclerosis but measurement of carotid intima thickness by ultrasonography is a non invasive and quantitative method of evaluating early atherosclerosis. The aim of this study was to assess carotid artery intima media thickness and to assess any correlation between carotid artery intimal thickness and coronary artery disease in Type II DM. This study was carried out in the department of medicine, Dr. Baba saheb Ambedkar hospital, Delhi to assess carotid intima media thickness (CIMT) as a risk factor for CAD in type II diabetes using Ultrasound B scan to assess CIMT. In this study, 30 patients of DM type II with CAD, 30 patients of DM type II without CAD & 30 patients were age and sex matched controls who did not have any disease. Mean CIMT was found to be significantly increased in DM type 2 with CAD group as compared to DM type 2 without CAD and the difference was found to be statistically significant (P<0.001). Also the mean CIMT was significantly increased in DM type 2 with and without CAD as compared to controls and the difference was statistically significant. Also, patients with more than 3 cardiovascular risk factors had significantly greater CIMT than patients who had less than 3 cardiovascular risk factors and the difference was statistically significant.

Cardiovascular risk and mannose binding lectin in patients with rheumatoid arthritis from southern Brazil

BackgroundMannose binding lectin (MBL) appears to be involved in susceptibility to rheumatoid arthritis (RA), in the inflammatory process and in the genesis of atherosclerotic disease. ObjectiveTo study the association of MBL serum levels and its genotypic variation with carotid arteries intimal thickness (IMT) in RA patients from Southern Brazil. MethodsMBL serum levels, MBL2 genotyping and IMT were investigated in 90 RA patients along with their demographic, clinical and laboratory profile. MBL levels and MBL2 genotyping were evaluated in 90 healthy controls. ResultsA significant lower MBL serum concentration was observed in patients with RA in relation to controls (528 ng/mL vs 937.5 ng/mL, p = 0.05, respectively). The median IMT in RA patients was 0.59 mm (0.51 to 0.85 mm). There was no correlation between levels of MBL with disease activity, erythrocyte sedimentation rate, autoantibodies presence or IMT (p = NS). A weak and negative correlation was found between MBL and CRP levels (Rho = −0.24; p = 0.02;). The MBL2 variant at codon 54 (variant B) and HYPA haplotype were the most frequently observed in the RA sample (67.5% and 31.7%). MBL2 wild type (A/A) were associated with lower IMT when compared with heterozygotes (A/O; p = 0.04) and low producers (O/O; p = 0.05). In addition, high producers genotypes had lower levels of CRP when compared with medium (p = 0.04) or with low producers (p = 0.05). ConclusionRA patients had lower MBL levels than controls. MBL were negatively associated with CRP serum levels; low MBL genotypes producers increased thickness of the IMT than high producers.

Differences in Risk Factor Profile between Carotid Intimal Medial Thickness and Pulse Wave Velocity in African-Americans with Type 2 Diabetes

Background: Diabetes is a robust risk factor for cardiovascular events which is marked in African Americans for reasons that may be attributed to socioeconomic and biologic vulnerabilities. Both structural (arterial thickening) and functional (arterial stiffness) abnormalities of the vasculature are predictive of incidental clinical events. Study objective was to determine the risk factors and relationship between large artery stiffness and carotid intimal thickness in African Americans with type II diabetes. Methods: 125 patients with diabetes were recruited from medical clinics. Medical information was obtained via interview and electronic medical record review. Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV) using applanation tonometry. Carotid Intimal Medial Thickness (CIMT) was obtained using B-mode ultrasound image analysis of the common carotid artery. Statistical analysis was done using SPSS version 23. Results: Mean age 60±8 years, 64% female. 82% hypertension, dyslipidemia 83%, diabetes duration 10.2±7.6 years, Mean HbA1C= 8.1±2.2%. Mean CIMT=0.68±0.15, PWV= 8.6±2.9. There was no significant association between PWV and CIMT. CIMT positively correlated with gender (r=0.302, p=0.001), smoking (r=0.278, p=0.002), creatinine (r=0.260, p=0.006), triglycerides (r=0.279, p=0.002), pooled cohort score (r=0.353, p=0.001), and negatively with HDL (r= -0.196, p=0.031). PWV positively correlated with creatinine (r=0.300, p=0.001), duration of diabetes (r=0.195, p=0.037) and age (β=0.359, p&amp;lt;0.0001) and pooled cohort score (r=0.248, p=0.003). After adjusting for cardiovascular risk factors, gender (β=-2.000, p=0.019), and age (β=0.119, p=0.018) independently predict PWV but not CIMT. Conclusion: Our findings indicate that PWV and CIMT differ in risk factor profile in African Americans with type II diabetes mellitus. Further studies are needed to clarify mediating factors. Disclosure A. Eluwole: None. A.M. Adedayo: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck &amp; Co., Inc.. C. Brown: None. M. Salifu: None. A. Bakillah: None. J. Lazar: None.

HIV related stigma, perceived social support and risk of premature atherosclerosis in South Asians

ObjectiveThis study sought to determine the association between social support and stigma experienced by HIV-positive patients and presence of subclinical cardiovascular disease. MethodsWe implemented a cross sectional study in 67 HIV-positive patients and 52 controls from a community health care center in central India. The participants underwent an in-depth survey and a clinical and laboratory assessment of cardiovascular risk. Carotid-intimal thickness (CIMT) was used as a marker of subclinical cardiovascular disease. ResultsOn comparing the HIV and age and sex-matched control population, HIV patients had lower body weight (P=<0.001), and lower systolic blood pressures (P=0.002). Despite the lack of higher cardiac risk factor prevalence and lower lipid abnormalities, HIV patients had higher right, left and average CIMT values than controls (P<0.001 for all). HIV patients also showed higher prevalence of abnormal CIMT (≥ 0.9mm) than controls (32% vs. 0%, P<0.001). HIV patients with increased CIMT (n=37) in comparison with those with normal CIMT (n=30) were more frequently males (P=0.023), had higher systolic blood pressures (P=0.002), lower CD4 counts (P=0.033) and experienced higher enacted stigma (P=0.044). On multivariable stepwise logistic regression, systolic blood pressure (odds ratio:1.06, P=0.002) and stigma score > 25th percentile value (odds ratio:3.84, P=0.037) were independent predictors of the abnormal CIMT. ConclusionsHIV-positive patients from central India have a higher prevalence of abnormal CIMT as a marker of subclinical cardiovascular disease than the general population. This predisposition to increased cardiovascular risk may be related to complex interactions between HIV disease and stigma-related healthcare inequalities.

Association of morning blood pressure surge with carotid intima-media thickness and cardiac dysfunction in patients with cardiac syndrome-X

Background & hypothesis: We hypothesized that exaggerated morning blood pressure surge, may contribute in cardiac dysfunction and arterial stiffness in patients with cardiac syndrome X. Thus we investigated the impact of morning blood pressure surge on cardiac function and carotid intima-media thickness in subjects with cardiac syndrome X.Methods: We studied patients with cardiac syndrome X using ambulatory blood pressure monitoring and investigated the association of morning blood pressure surge with carotid intima thickness, left atrial volume index and left ventricular filling (E/e'). Seventy patients with cardiac syndrome X were enrolled for the study and compared with 70 age and sex matched controls.Results: Patients with cardiac syndrome X were stratified based on the systolic morning blood pressure surge value of control subjects to patients with exaggerated blood pressure surge (n = 42) and those with normal morning blood pressure surge (n = 28). Basal heart rate (p < .05), high sensitive C-reactive protein (p < .01), left atrial volume index (p < .01), E/e' (p < .01); carotid intima-media thickness (p < .001) and percentage of detected plaque (p < .005) were significantly higher in patients with exaggerated morning blood pressure surge group than those with morning blood pressure surge group. Morning blood pressure surge was significantly correlated with carotid intima-media thickness, high sensitive C-reactive protein, left atrial volume index and E/e' ratio in patients with cardiac syndrome X. In multivariate analysis, exaggerated morning blood pressure surge was the only independent predictor of increased carotid intima-media thickness (OR = 2.379; p < .001), and diastolic dysfunction (OR = 2.464; p < .001) in patients with cardiac syndrome X.Conclusion: Our data suggest that excessive morning blood pressure surge is an independent predictor for arterial stiffness and diastolic dysfunction in patients with cardiac syndrome X.

Orthostatic Hypotension and Risk of Clinical and Subclinical Cardiovascular Disease in Middle-Aged Adults.

BackgroundAlthough orthostatic hypotension (OH) is a well‐recognized manifestation of neuropathy and hypovolemia, its contribution to cardiovascular disease (CVD) risk is controversial.Methods and ResultsParticipants with OH, defined as a decrease in blood pressure (systolic ≥20 mm Hg or diastolic ≥10 mm Hg) from the supine to standing position, were identified during the first visit of the ARIC (Atherosclerosis Risk in Communities) Study (1987–1989) within 2 minutes of standing. All participants were followed up for the development of myocardial infarction, heart failure, stroke, fatal coronary heart disease (CHD), any CHD (combination of silent, nonfatal, and fatal CHD or cardiac procedures), and all‐cause mortality. Participants were assessed for carotid intimal thickness and plaque during the first visit. Detectable high‐sensitivity troponin T (≥5 ng/L) and elevated NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; ≥100 pg/mL) were determined in blood collected during the second visit (1990–1992). All associations were adjusted for known CVD risk factors. In 9139 participants (57% women; 23% black; mean age, 54±5.7 years), 3% had OH. During follow‐up (median, 26 years), OH was associated with myocardial infarction (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.44–2.46), congestive heart failure (HR, 1.65; 95% CI, 1.34–2.04), stroke (HR, 1.83; 95% CI, 1.35–2.48), fatal CHD (HR, 2.77; 95% CI, 1.93–3.98), any CHD (HR, 2.00; 95% CI, 1.64–2.44), and all‐cause mortality (HR, 1.68; 95% CI, 1.45–1.95). OH was also associated with carotid intimal thickness (β, 0.05 mm; 95% CI, 0.04–0.07 mm), carotid plaque (odds ratio, 1.51; 95% CI, 1.18–1.93), detectable high‐sensitivity troponin T (odds ratio, 1.49; 95% CI, 1.16–1.93), and elevated NT‐proBNP (odds ratio, 1.92; 95% CI, 1.48–2.49).Conclusions OH identified in community‐dwelling middle‐aged adults was associated with future CVD events and subclinical CVD. Further research is necessary to establish a causal role for OH in the pathogenesis of CVD.

Is increased uric acid a risk factor or a defensive response? The Campania Salute Network

Background and aimsCirculating uric acid (UA) is positively associated with body mass index (BMI), blood glucose, blood pressure (BP), markers of inflammation, and altered lipid profile. UA has also anti-oxidative properties which might be beneficial for cardiovascular (CV) system. It is still debated whether or not UA is independently associated with increased CV morbidity and/or mortality. Methods and resultsWe studied prognostic impact of UA in 8833 hypertensive adults (mean age 53 ± 12 yrs, 3857 women) from the Campania Salute Network, without prevalent CV disease and more than stage 3 CKD. We calculated standardized UA Z-score, adjusted for age, sex, glomerular filtration rate, and BMI. Low and high UA and UA Z-score quartiles were compared to the 2 middle quartiles assumed to be “normal”. Prevalence of obesity and diabetes was higher in low and high than in normal UA Z-score group (all p < 0.001). Systolic BP, left ventricular mass, carotid intima thickness were significantly higher and ejection fraction was reduced in the presence of high UA Z-score (all p < 0.001). Over 33-months average follow-up, incident major CV end-points (MACE) were not significantly different among low, normal and high UA or UA Z-score. In the latter analysis, however, incident MACE tended to be more frequent in the low than the high UA Z-score. Despite the results of multivariable analyses, the effect of less aggressive therapy in low UA Z-score cannot be excluded with certainty. ConclusionIn treated hypertensive patients, high levels of UA normalized for major biological determinants do not independently predict CV outcome. ClinicalTrials.gov IdentifierNCT02211365.

Abstract 044: Platelet-Endothelial Interactions in Atherosclerosis-Prone Arteries in a Non-Human Primate Model of Obesity and Insulin Resistance

Background: Platelet interactions with the vascular endothelium contribute to early atherogenesis, and occur in part from oxidative stress and secondary dysregulation of endothelial-associated von Willebrand factor (VWF). We used in vivo contrast enhanced ultrasound (CEU) molecular imaging of the carotid endothelium in a non-human primate model of diet-induced obesity to test whether platelet adhesion is present in atherosclerosis-susceptible arteries prior to plaque development, and whether it can be modified through NADPH-oxidase (Nox) inhibition. Methods: Six adult rhesus macaques fed a high-fat diet (HFD), with 30% of calories from fat, for &gt;2 years were studied at baseline and after 8 weeks of therapy with the Nox inhibitor apocynin (50 mg/kg/d). Six lean chow-fed controls were also studied. Intravenous glucose tolerance tests (IVGTT) and body composition were assessed at each interval. CEU molecular imaging of VCAM-1 and platelet GPIbα of the carotid arteries bilaterally was used to assess endothelial activation and platelet adhesion. Carotid intimal thickening (IMT) and brachial flow-mediated dilation (FMD) were assessed by ultrasound. Results: Before therapy, animals on HFD compared to controls were obese (16.0 vs 9.3 kg, p=0.003), had increased visceral adiposity (49% vs 25% truncal fat, p=0.002), and were insulin resistant (4-fold higher insulin AUC on IVGTT, p=0.002). FMD and IMT were similar between cohorts, although mild plaque was seen in the carotid bulb in 3 HFD macaques. HFD animals had greater (p&lt;0.01 vs. controls) carotid CEU signal for VCAM-1 (20.0 vs -2.7 IU) and GPIbα (12.7 vs -0.4 IU). There was a linear correlation between VCAM-1 and GP1ba signal (r 2 =0.50, p=0.0001). Apocynin significantly reduced (p&lt;0.01 vs pre-treatment) signal for VCAM-1 (3.96 IU) and GPIbα (0.19 IU); but did not alter IMT, FMD, visceral adiposity, or insulin resistance on IVGTT. Conclusions: Platelet- endothelial interactions occur early in atherosclerosis-prone carotid arteries of obese and insulin resistant non-human primates, and correlates with the degree of endothelial adhesion molecule expression. Inhibition of Nox suppresses platelet adhesion and reduces VCAM-1 expression independent of any effects on insulin resistance and obesity.

Comparative burdens of atherosclerosis in rural and urban communities in South India: Insights from the Kovai Medical Center and Hospital-noncommunicable disease studies

Aim: The aim of this study was to describe the distribution and comparison of carotid intima thickness in two completely different demographics in South India. Materials and Methods: Data were obtained from 865 participants in rural Nallampatti and 1081 participants from urban Kalapatti in the state of Tamil Nadu. Local ethics committee approval and written and informed consent were obtained from all participants. Carotid intima thickness was measured on all participants using high-resolution B-mode ultrasound. Atherosclerosis was defined as a carotid intima-media thickness of ≥1 mm. Results: The prevalence of atherosclerosis was 10.3% in rural Nallampatti compared to 7.8% in urban Kalapatti. On binary logistic regression analysis, diabetes and hypertension were associated with atherosclerosis in rural areas, but this significance disappeared after adjustment for confounding factors. In urban areas, diabetes appeared to be significantly associated with atherosclerosis even after adjustment for confounding factors. Conclusion: Our data suggest a surprisingly increased prevalence of atherosclerosis in a rural farming population even though traditional risk factors for atherosclerosis such as diabetes and hypertension did not show a significant association after adjustment for confounding factors. If confirmed, this provides a rationale to do large-scale studies to explore the role of nontraditional risk factors in rural India that could have an impact on atherosclerosis and cardiovascular disease.

Abstract P365: Objectively Measured Snoring is Associated with Carotid Vascular Remodeling in Overweight and Obese Adults

Introduction: Snoring is often used as a surrogate measure for obstructive sleep apnea (OSA), a sleep disorder associated with elevated cardiovascular disease (CVD) risk. Although the literature supports a link between snoring and CVD, it is not clear if this association is independent of OSA. The objective of our study was to explore the association between snoring and subclinical CVD in adults with and without OSA. We hypothesized that snorers would have a greater burden of subclinical CVD, including thicker carotid intima media thickness (CIMT) and higher pulse wave velocity (PWV). Methods: Cross-sectional analyses were conducted using 24-month follow up data from the Slow Adverse Vascular Effects (SAVE) study, a randomized controlled trial evaluating the effects of weight loss, increased physical activity, and reduced dietary sodium intake on vascular health. The original population included 349 men and women aged 20-45 years and BMI 25-40 kg/m 2 . Participants (n=122) with objective measures of sleep-disordered breathing from a home-based sleep assessment (ResMed ApneaLink) were grouped into three categories using the snoring index (SI) and oxygen desaturation index (ODI). SI is defined as the number of vibratory snoring events per hour of recording time . ODI is the number of oxyhemoglobin desaturations of ≥ 4% per hour of recording . The snoring categories were: OSA (ODI≥5; n=41), heavy snoring (ODI&lt;5, above-median SI; n=40), and normal snoring (ODI&lt;5, below-median SI; n=41). Vascular measures such as carotid-femoral PWV (cfPWV), femoral-ankle PWV (faPWV), brachial-ankle PWV (baPWV), CIMT, and carotid inter-adventitial diameter were compared across snoring groups. We used multiple linear regression to assess the association between snoring and subclinical CVD independent of age, sex, BMI, mean arterial pressure, and intervention group. Results: Participants were on average 40.1 ± 5.9 years old (BMI of 31.6 ± 4.4 kg/m 2 ; 76.2% women and 82% white). Across snoring severity categories, most CVD risk factors worsened including age, blood pressure, BMI, lipids, and fasting glucose (ANOVA; all p &lt;.05). Similarly, vascular measures including faPWV, baPWV, CIMT, inter-adventitial diameter and bulb IMT differed across snoring categories with differences occurring mainly between the normal snoring and OSA groups. Differences in carotid inter-adventitial diameter and CIMT were noted between normal and heavy snoring groups (6.52 ± 0.49 vs. 6.83 ± 0.49; 0.58 ± 0.06 vs. 0.63 ± 0.07; mm), respectively. Following covariate adjustment, differences in carotid inter-adventitial diameter and IMT persisted between normal and heavy snoring categories (p &lt;.05). Conclusion: Our findings suggest that, in overweight and obese adults, objectively measured snoring is related to indices of local vascular remodeling and aging, even in those without OSA. Snoring severity may be associated with CVD risk.

The effect of cardiovascular risk factors on the carotid intima-media thickness in an old-aged cohort with hypertension: a longitudinal evolution with 4-year follow-up of a random clinical trial

ABSTRACTHypertension is a generally accepted atherogenic risk factor. The aim of this prospective longitudinal study was to evaluate changes in carotid intima-media thickness (c-IMT) and explore the association of cardiovascular risk factors and the carotid intima thickness in adults with hypertension using standardized methods. We used data from a subgroup of Beijing Vascular Disease Patients Evaluation Study (BEST), a population-based study of community-dwelling adults. The c-IMT, biomarkers, and carotid-femoral-pulse wave velocity (PWV) were measured at baseline, and lifestyles such as smoking status, sleeping habits, and oil or salt intake level were determined with the use of a validated questionnaire in the follow-up. We reevaluated c-IMT in all the initial 1284 (540 female and 744 male) patients with hypertension after 4 years. At reevaluation, mean (± SD) age was 66 ± 1.2 years, systolic blood pressure was 138 ± 19 mmHg, and diastolic blood pressure was 91 ± 10 mmHg. The results showed that mean c-IMT z-scores increased significantly during 4 years (0.002 ± 0.003, p < 0.001) as well as carotid-femoral PWV (13.99 ± 2.74, p < 0.01) and total cholesterol (6.97 ± 1.08, p < 0.001). Linear regression showed statistically significant associations between systolic blood pressure, diastolic blood pressure, C-reactive protein, lip-line, and heart rate with c-IMT z-scores of >1.5SD in the fully adjusted models and the p values were 0.000, 0.000, 0.017, 0.001, and 0.044, respectively . There were significant predictors for the mean effect on c-IMT z-score. In a full-model logistic regression, significant risk factors for an increase in IMT of ≥1.5 z-scores were carotid-femoral PWV (odds ratio: 1.119, confidence interval: 1.018, 1.230, p = 0.020 < 0.05) at first measurement. The conclusion of the study was that longitudinal c-IMT measurements revealed progression in subclinical atherosclerosis during a four-year period in a hypertensive old-aged cohort. Systolic or diastolic blood pressure, homocysteine, carotid-femoral PWV, and waistline were significantly related to c-IMT increment. By lifestyle and medical intervention to control these risk factors may prevent progression of c-IMT in old-aged cohort with hypertension.Clinical trial registration: Clinical trials. Gov. Identifier: NCT02569268.

Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART): study protocol for a randomized controlled trial

BackgroundThere is an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA). Secondary prevention guidelines recommend that antihypertensive, statin and antiplatelet therapy be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular-risk reduction. However, these goals are seldom realized in routine clinical care settings in SSA due to logistical challenges.We seek to assess whether a polypill containing fixed doses of three antihypertensive agents, a statin and antiplatelet therapy taken once daily per os for 12 months among recent stroke survivors would result in carotid intimal thickness regression compared with usual care (UC).MethodsThe Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is a phase 2, open-label, evaluator-blinded trial involving 120 Ghanaian recent-ischemic-stroke survivors. Using a computer-generated sequence, patients will be randomly allocated 1:1 into either the intervention arm or UC. Patients in the intervention arm will receive Polycap DS® (containing aspirin, 100 mg; atenolol, 50 mg; ramipril, 5 mg; thiazide, 12.5 mg; simvastatin, 20 mg) taken as two capsules once daily. Patients in the UC will receive separate, individual secondary preventive medications prescribed at the physician’s discretion. Both groups will be followed for 12 months to assess changes in carotid intimal thickness regression – a surrogate marker of atherosclerosis – as primary outcome measure. Secondary outcome measures include adherence to therapy, safety and tolerability, health-related quality of life, patient satisfaction, functional status, depression and cognitive dysfunction.DiscussionAn efficacy-suggesting SMAART trial could inform the future design of a multi-center, double-blinded, placebo-controlled, parallel-group, randomized controlled trial comparing the clinical efficacy of the polypill strategy for vascular risk moderation among stroke survivors in SSA.Trial registrationClinicalTrials.gov, ID: NCT03329599. Registered on 11 February 2017.

Impact of different antihypertensives on carotid arterial wall thickness.

Hypertension has been associated with atherosclerosis and cardiovascular disease. Carotid intima media thickness is increased in hypertensive patients. But, the correlation between carotid intima media thickness and antihypertensive agents is still uncertain. Therefore, we investigated carotid intima media thickness based on types of antihypertensive agents. 1809 patients were enrolled in this study and it showed that 1079 hypertensive patients had thicker carotid intima media thickness than non-hypertensive patients, with carotid intima media thicknesses of (0.72±17mm vs 0.64±15mm, P<.001), (0.31±0.07mm vs 0.30±0.06mm, P<.001), and (0.41±0.13mm vs 0.35±0.12mm, P<.001). Additionally, hypertensive patients on beta-blockers also had thicker carotid intima media thickness than the non-beta-blocker group, with carotid intima media thicknesses of (0.74±0.18mm vs 0.71±0.16mm, P=.018), (0.33±0.09mm vs 0.31±0.07mm, P=.029), and (0.43±0.13mm vs 0.40±0.13mm, P=.035). Multivariate analysis showed that carotid intima thickness was only correlated with beta-blockers (odds ratio=2.489, confidence interval=1.183-5.239, P=.016); however, this study showed that beta-blocker could be associated with increased carotid wall thickness as well.

Study of the osteoprotegerin/receptor activator of nuclear factor-kB ligand system association with inflammation and atherosclerosis in systemic sclerosis

ABSTRACT Objective we aimed to study systemic sclerosis patients in order to assess osteoprotegerin/Receptor activator of nuclear factor-kB ligand (OPG/RANKL) system and find the relation of these biomarkers with the clinical features of the disease, the carotid intima thickness, markers of inflammation, lipid profile, and other laboratory characteristics. Methods both the level of (RANKL), (OPG) in sera of participants, in 30 (SSc) patients and the atherosclerotic changes affecting the common carotid artery were measured and, were compared to 30 healthy controls matched for age and sex. All participants were assessed clinically and subjected to the Revised Medsger SSc severity scale and underwent carotid Doppler ultrasound examination. Results OPG, RANKL, and RANKL/OPG were 1.9 ± 0.4 ng/ml, 24.3 ± 17.25 ng/ml, and 13.5 ±9.8 versus 0.77 ± 0.25 ng/ml, 7.13 ± 3.02 ng/ml, and 9.6 ± 3.1 in the SSc patients and the controls with significance (P = 0.001, P = 0.001, P = 0.045) respectively. The OPG- RANKL axis in the SSc patients correlated significantly with carotid intima thickness, arthritis, arthralgia, inflammatory markers, Medsger joint, Medsger vascular, Medsger skin, and dyslipidemia. Conclusion In cardiovascular risks, OPG serum level might increase as a preventive compensatory mechanism to neutralize the RANKL level increment. The determination of the OPG-RANKL system is a diagnostic indicator for the intensity of vascular calcification and atherosclerosis in SSc patients.