Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Study of Carotid Intima Media Thickness (CIMT) In Type 2 Diabetes Mellitus and Its Correlation with Glycaemic Control and Inflammatory Marker HsCRP

Background: Carotid Intima Media Thickness (CIMT) andCRP (C Reactive Protein) are have been used for measuringAtherosclerotic Risk in Diabetics. However there is paucity ofdata regarding their importance in Statin Naïve Diabetics.Aim: To study Correlation of CIMT with glycaemic control andhsCRP in Statin Naïve Diabetics.Materials and Methods: 80 Cases (Patient suffering from type2 Diabetes Mellitus) and 20 controls (non- diabetic healthpatients) presenting in outpatient department of a tertiaryHospital were included in this observational cross sectionalobservational study. Complete Blood Count, urine Routine andMicroscopy, urine for microalbuminuria, fasting plasma glucose(FPG), postprandial plasma glucose (PPPG), glycatedhaemoglobin (HbA1C), lipid profile, renal function test, hs-CRPand CIMT were evaluated in each individual. Independentsamples T-test was used to compare CIMT and hs-CRP bothcases and controls. Test of proportion and chi-square test wasused for association between categorical variables.Spearman’s method was used to assess correlation betweenhsCRP and CIMT.Results: 80 cases (Statin naïve and Non-smoker Diabeticpatients and 20 healthy controls were included in this study.Average CIMT in cases was significantly higher in Diabeticcases than Control (0.66 + 0.14 vs 0.56±0.05, difference= 0.10 mm, 95% C.I. (0.1 - 0.17), p < 0.0001). HsCRP wassignificantly correlated with average CIMT in Diabetic cases.(r=0.512, 95% C.I. 0.33-0.658, p<0.0001). Fasting Blood Sugarwas correlated with average CIMT in Diabetic cases. (r=0.234,95% C.I. 0.015-0.432, p=0.0366). Post Prandial Blood Sugarwas also correlated with average CIMT (r=0.300, 95% C.I.0.086-0.488, p=0.00677).Conclusion: Cardiovascular risk factors like glycaemic controland inflammatory markers like hsCRP are significantlyassociated with CIMT even in non-smoking and statin naïveDiabetics.

Correlation between serum 25-hydroxyvitamin D levels and carotid intima-media thickness in a Brazilian population descended from African slaves

Hypovitaminosis D has been identified as a possible new cardiovascular risk factor. However, the results of studies correlating serum vitamin D levels with markers of subclinical atherosclerosis have been conflicting. The aim of this study was to correlate serum levels of 25-hydroxyvitamin D [25(OH)D] with carotid intima-media thickness (C-IMT) and conventional cardiovascular risk factors in Afro-descendants. A cross-sectional analysis was performed on a sample of 382 individuals from a cohort of descendants of African slaves, inhabitants of "Quilombola" communities, with a mean age of 57.79 ±15.3 years, 54.5% of whom were women. Socio-demographic and clinical data were collected and biochemical tests were performed, including serum levels of 25(OH)D by electrochemiluminescence and urinary albumin excretion, evaluated by the albumin/creatinine ratio (ACR) in a spot urine sample. All participants underwent high-resolution ultrasonography for C-IMT measurement. Hypovitaminosis D was defined as serum 25(OH)D levels <30 ng/mL. The mean serum 25(OH)D levels were 50.4±13.5 ng/mL, with a low prevalence of hypovitaminosis D (4.86%). By simple linear correlation, a significant inverse association between 25(OH)D levels and C-IMT (r=-0.174, P=0.001) was observed. However, after multiple linear regression analysis, the significance of the association between serum levels of 25(OH)D and C-IMT measurement was lost (β=-0.039, P=0.318) and only male gender, age, smoking, systolic blood pressure, glucose and low density lipoprotein (LDL)-cholesterol remained significantly associated with C-IMT. Levels of 25(OH)D were independently and positively associated with HDL-cholesterol and inversely associated with age and ACR. In conclusion, no independent association between 25(OH)D levels and C-IMT was observed in this population. On the other hand, there was an inverse association with albuminuria, a marker of endothelial lesion.

Effects of Methotrexate on Carotid Intima-media Thickness in Patients with Rheumatoid Arthritis

The purpose of this study was to evaluate the effects of rheumatoid arthritis (RA) and antirheumatic drugs on atherosclerosis by comparing carotid intima-media thickness (CIMT) as an indicator for cardiovascular diseases (CVD). This study included 44 female RA patients who met the 2010 ACR/EULAR criteria and age-matched 22 healthy females. CIMT was measured on both carotid arteries using a B-mode ultrasound scan. The mean value of both sides was taken as the CIMT of the subject. The CIMT was evaluated according to the use of drugs, disease activity and CVD risk factors in RA patients as a case-control study. Higher CIMT was observed in RA patients as compared with healthy subjects (0.705 +/- 0.198 mm, 0.611 +/- 0.093 mm, respectively, P < 0.05). With adjustment for the CVD risk factors, disease activity and the use of anti-rheumatic drugs, methotrexate (MTX) only showed a favorable effect on CIMT in RA. A significantly lower CIMT was observed in RA with MTX as compared with RA without MTX (0.644 +/- 0.136 mm, 0.767 +/- 0.233 mm, respectively, P < 0.05). The effects were correlated with MTX dosage (beta = -0.029, P < 0.01). The use of MTX should be considered in high priority not only to control arthritis but also to reduce the RA-related CVD risk to mortality.

Correlation of Coronary Angiographic Severity with Carotid intima Media Thickness and Flow mediated dilatation of brachial Artery in Patients with Ischemic Heart Disease.

Background: Ischemic Heart Disease which encompasses Acute Coronary Syndrome and Chronic Stable Angina is the most common cause of worldwide mortality and morbidity. Carotid intima media thickness (CIMT) is a non-invasive ultrasonographic technique to image the carotid arteries which measures the thickness of the intima and media of these vessels. It is a marker of atherosclerotic process. Flow mediated dilatation (FMD) is a marker of endothelial function of arteries. Ischemic heart disease can be predicted long before its actual occurrence by observing these two phenomenons. Methods: This cross sectional study done in the Department of Cardiology, Dhaka Medical College Hospital during the period of Oct 2010- Sept 2011.We enrolled 102 patients admitted with IHD by purposive sampling. We assessed FMD of brachial artery, CIMT by vascular duplex. Coronary artery disease severity was assessed by vessel score, stenosis score and extent score from angiography. Results:The mean (±SD) age of the patients was 50.9(±11.3) years. The male- female ratio was 5:1. CIMT has significant negative correlation with FMD (r=-.407, p=<.001). Flow mediated dilatation of brachial artery has weak but significant negative co-relation with vessel score(r=-.609, p=<.001), stenosis score(r=- .493, p=<.001) and extent score (r=-.477, p=<.001). However, carotid intima media thickness has weak but positive correlation with vessel score (r=.447, p=<.001), stenosis score (r=.417, p=<.001) and extent score(r=.412, p=<.001). Conclusion: The present study concludes CIMT has significant negative correlation with flow mediated dilatation of brachial artery. FMD has weak but significant negative co-relation and CIMT has weak but positive correlation with vessel score, stenosis score and extent score of coronary arteries.

Intima-Media Thickness and Pulse Wave Velocity in Hypertensive Adolescents

Increased intima-media thickness (IMT) and pulse wave velocity (PWV) are noninvasive markers of early arterial wall alteration and are more widely used in adult clinical research. We investigated whether IMT and PWV are useful predictors of cardiovascular risk in hypertensive adolescents. Fifteen hypertensive adolescents (13-18 yr old, systolic BP > or = 140 mmHg, diastolic BP > or = 90 mmHg) and seventeen normotensive subjects were included. Height, weight, obesity index, body mass index (BMI), and fat distribution were obtained from each group. Serum lipid, insulin, vitamine B12, folate, renin, aldosterone, angiotensin-converting enzyme (ACE), and homocysteine levels were compared. The carotid IMT and PWV were measured. Arterial wall compliance and distensibility were calculated with the equation. High systolic blood pressure significantly correlated with height, weight, BMI, obesity index, arm circumference, fat mass, and fat distribution. Hypertensive adolescents had significantly greater cIMT (carotid intima-media thickness) and lower elastic properties such as cross-sectional compliance and distensibility of the carotid artery. The carotid IMT significantly correlated with brachial-ankle PWV. In conclusion, the measurement of carotid IMT and brachial-ankle PWV might be useful to predict the development of atherosclerosis in hypertensive adolescents.