Surrogate Marker Of Atherosclerosis Research Articles

Ischemic Stroke and its Association with Risk Factors at Nepalgunj Medical College Teaching Hospital Kohalpur

Introduction: Incidence of stroke increases with age and growing elderly population worldwide, the number of patients with stroke are likely to increase. It is the third most common cause of death in world in that 85% are ischemic in nature. Atherosclerosis is a major risk factor in cerebrovascular diseases. Carotid Intima Media thickness (CIMT) is a surrogate marker of atherosclerosis and provides a non-invasive method for the risk assessment of cerebrovascular diseases.
 Aims: To study the atherosclerotic risk profile of patients admitted with ischemic stroke in medical ward with study of the carotid artery intima-media thickness in patients with acute ischemic stroke.
 Methods: 92 patients with ischemic strokes were studied in this observational study. Carotid Doppler was performed in all patients with emphasis on carotid artery stenosis and intima thickening. Analysis of Association of various risk factors was done in detail. Study period was from June 2019 to May 2020.
 Results: Higher degree of stenosis was associated with hypoechoic plaques and cortical strokes. Hypertension was the most common and most significant risk factor. Multiple risk factors also appear to have synergistic actions.
 Conclusion: Various modifiable risk factors provide valuable target for primary and secondary prevention of stroke. Carotid Doppler is a very cheap and highly effective tool for further management of stroke patients. Most of the asymptomatic patients, risk factors may warrant precautionary carotid Doppler, and may result in significant reduction in disease burden on the families and the community and should be encouraged.

Lipid effects of glucagon-like peptide 1 receptor analogs.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming more prominent as a therapeutic choice in diabetes management and their use is being expanded to other indications, such as obesity. Dyslipidemia and cardiovascular disease are common co-morbidities in these populations and understanding the impact of this class of medications on the lipid profile may be an important consideration. Several GLP-1RAs trials demonstrate them to be safe and potentially beneficial for cardiovascular outcomes; improvements in surrogate markers of atherosclerosis have also been observed. Lipid data collected as secondary outcomes from large clinical trials as well as some smaller dedicated trials show that GLP-1RAs can modestly lower low-density lipoprotein (LDL) and total cholesterol (C), and most show modest fasting triglyceride (TG) lowering. Effects on high-density lipoprotein-C have been less consistent. Some have also demonstrated substantial blunting of the postprandial rise in serum TGs. Favorable effects on lipoprotein metabolism, with reduced levels of small dense LDL particles and decreased atherogenic potential of oxidized LDL, have also been seen. Mechanisms underlying these observations have been investigated. This review summarizes the data available on the lipid effects of GLP-1RAs, and explores the current understanding of the mechanisms underlying these observed effects.

57-OR: Predictive Role of Atherosclerosis Biomarkers on Carotid Plaque Extension in Type 2 Diabetes

Matrix metalloproteinases (MMP) and tumor necrosis factor receptor superfamily members have been recently proposed as surrogate markers of atherosclerosis in the general population. The aim of this study was to examine their predictive role in type 2 diabetes (T2D). Plasma levels of MMP-12, MMP-7, CD40 and its ligand (CD40-L) were measured by Proximity Extension Assay in a well-characterized cohort of 1,144 patients with carotid atherosclerosis from the SUMMIT study (age= 69 [64 - 75], males 66.7%, T2D 66.5%). Carotid plaque area was measured by plaque contours using the ultrasound trace function. The associations were adjusted for age, sex, waist, hypertension, history of cardiovascular diseases (CVD), smoke load, plasma triglycerides, LDL-cholesterol (LDL-c) and HDL-cholesterol (HDL-c), and serum creatinine levels. All measured biomarkers were associated with carotid plaque area, independently of potential confounders, with CD40 showing the strongest effect and MMP12 showing a significant interaction with T2D. In subgroup analyses, the effect of MMP-12 and MMP-7 remained significant only in T2D, while the effect of CD40 and CD40-L was similar in both subgroups. This study demonstrates the ability of MMP-12, MMP-7, CD40, and CD40-L in predicting carotid atherosclerotic burden in a population at high cardiovascular risk and identifies MMP-12 as a specific biomarker for T2D. Disclosure S. Leonetti: None. D. Trico: None. I. Goncalves: None. A. Shore: None. F. Khan: None. J. Nilsson: None. A. Natali: None. Funding Innovative Medicines Initiative (IMI-2008/115006)

FMD and CIMT: Surrogate Markers of Atherosclerosis in Subclinical and Overt Hypothyroidism in Sub Himalyan Region.

Introduction:Hypothyroidism increases the risk of atherosclerosis. Carotid intima-media thickness (CIMT) and flow-mediated dilation (FMD) have been used as a noninvasive method to detect atherosclerosis. But the literature is scarce on patients with subclinical hypothyroidism. Such a study was not done in our region, so we conducted this study at a tertiary care center to compare CIMT and FMD among subclinical and overt hypothyroid patients and to analyze the risk of atherosclerosis.Methods:We evaluated 68 patients aged 18–50 years, with newly diagnosed hypothyroidism. We divided them into overt and subclinical hypothyroidism groups and compared the findings. All analyses were performed by the computerized SPSS 17.0. The results were noted as means ± SD and percentage. Student's t-test was used to compare continuous variables, and the Chi-square test was used to compare differences.Results:The total number of patients with dyslipidemia in the subclinical hypothyroidism (SCH) group was 22 (45.83%) and in the overt hypothyroidism (OH) group was 26 (54.16%) with a P- value of 0.009. The mean FMD% in subclinical hypothyroidism patients was 6.9816 ± 3.4224 and in overt hypothyroidism patients was 5.3670 ± 2.7278 (P = 0.03). The mean CIMT was 0.5009 ± 0.0732, CIMT in the SCH group was 0.5082 ± 0.0672 and in the OH group was 0.5305 ± 0.0799 (P = 0.2).Conclusion:The outcome of this study specifies that hypothyroidism is associated with endothelial dysfunction as established by impaired FMD, and it may be the first marker of atherosclerosis appearing before any structural evidence like CIMT. We can speculate that there is a link between subclinical hypothyroidism and atherosclerosis, and thyroxine replacement in SCH may help to prevent the progression of atherosclerosis.

Association between popliteal artery wall thickness and structural progression in individuals with symptomatic knee osteoarthritis

Purpose: Osteoarthritis is the most prevalent chronic joint disorder with multifactorial aetiologies. There has been evidence for the involvement of vascular pathology in the progression and development of knee osteoarthritis. Increased popliteal artery wall thickness has been shown to be a risk factor for cardiovascular disease, being used as a surrogate marker of atherosclerosis. Previous studies have shown associations between increased popliteal artery wall thickness and adverse knee structural changes in community-based adults without clinical knee osteoarthritis.

Elevated Serum Concentrations of Remnant Cholesterol Associate with Increased Carotid Intima-Media Thickness in Children and Adolescents

To evaluate the relationship between remnant cholesterol and carotid intima-media thickness (cIMT), a surrogate marker for atherosclerosis, in children and adolescents. Anthropometric, laboratory, liver, and carotid ultrasonographic data were obtained from 767 youths (594, overweight/obese; 173, normal weight). Fasting remnant cholesterol was calculated from the standard lipid profile. cIMT ≥0.56mm (corresponding to the 90th percentile of values observed in normal-weight children) was chosen to define elevated cIMT. Logistic regression analysis was used to estimate the risk of elevated cIMT according to tertiles of remnant cholesterol levels. In the entire cohort, the mean concentration of remnant cholesterol was 17.9±10.3mg/dL and mean cIMT value was 0.51±0.8mm. Remnant cholesterol significantly correlated with age, sex, body mass index, waist circumference, blood pressure, lipids, liver enzymes, and insulin resistance. cIMT value increased progressively with rising remnant cholesterol tertiles (Pfor trend<.001). Compared with subjects in the lowest remnant cholesterol tertile, those in the middle and highest remnant cholesterol tertiles had a 2.3- and 2.4-fold increased risk of elevated cIMT, independently of age, sex, pubertal stage, body mass index, and apolipoprotein B (all Padj≤.003). When the effects of overweight/obesity on the association between remnant cholesterol and cIMT were determined, normal-weight as well as overweight/obese subjects in the highest remnant cholesterol tertile had a 3.8- and 2.3-fold increased risk to have elevated cIMT compared with the respective study groups in the lowest tertile, after adjustment for conventional risk factors (Padj=.038 and Padj=.003, respectively). In youths, elevated levels of remnant cholesterol might represent a marker of early atherosclerotic damage.

The impact of particulate matter air pollution (PM2.5) on atherosclerosis in modernizing China: a report from the CATHAY study.

Air pollution has been associated with an increase in cardiovascular diseases incidence. To evaluate whether air pollution can accelerate atherogenic processes, we assessed the effects of air pollution on important surrogate markers of atherosclerosis [brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT)]. A total of 1656 Han Chinese (mean age 46.0 + 11.2 years; male 47%) in Hong Kong, Macau, Pun Yu, Yu County and the 3-Gorges Territories (Yangtze River) were studied between 1996 and 2007 [Chinese Atherosclerosis in the Aged and Young Project (the CATHAY Study)]. Cardiovascular risk profiles were evaluated. Particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) parameters were computed from satellite sensors. Brachial FMD and carotid IMT were measured by ultrasound. Health parameters [age, gender, body mass index, waist : hip ratio (WHR) and glucose)] were similar in lowest and highest PM2.5 exposure tertiles, systolic and diastolic blood pressures and triglycerides were higher (P < 0.001) and low-density cholesterol (LDL-C) was lower in the top PM2.5 tertile (P < 0.001). Brachial FMD [7.84 ± 1.77, 95% confidence interval (CI) 7.59-8.10%, vs 8.50 ± 2.52, 95% CI 8.23-8.77%, P < 0.0001) was significantly lower and carotid IMT (0.68 ± 0.13 mm, 95% CI 0.67-0.69 mm vs 0.63 mm ± 0.15 mm 95% CI 0.62-0.64 mm; P < 0.0001) was significantly thicker in the top PM2.5 tertile compared with the lowest tertile. On multiple regression, FMD was inversely related to PM2.5 (beta = 0.134, P = 0.015) independent of gender, age and blood pressure (model R2 = 0.156, F-value = 7.6, P < 0.0001). Carotid IMT was significantly correlated with PM2.5 exposure (beta = 0.381, P < 0.0001) independent of age, location, gender, WHR, blood pressure and LDL-C (model R2 = 0.408, F-value = 51.4, P-value <0.0001). Air pollution is strongly associated with markers of early atherosclerosis, suggesting a potential target for preventive intervention.

Ideal Cardiovascular Health Index and Its Determinants in a Rural South African Population.

Background:The ideal cardiovascular health index (CVHI) is a measure to summarize cardiovascular (CV) health, and includes smoking, body-mass index, physical activity, blood pressure, glucose, total cholesterol, and diet.Objective:This study aimed to assess CV health using the CVHI and determinants on CV health in a rural African population, and correlate carotid intima-media thickness (CIMT), a surrogate marker for atherosclerosis, with CVHI.Methods:A cross-sectional analysis was performed on baseline data of the Ndlovu Cohort Study, located in rural South Africa. CVHI score (CVHIs) was calculated by the sum of favourable CVHI factors (range 0 to 7). Logistic regression was performed to examine the association of age, sex, HIV-status, education level, employment status, and income with good CV health (5–7 favourable health factors). Mean CIMT was displayed by poor, intermediate and good CV health.Results:The study included 1927 participants with a mean age of 38.7 years (SD ± 12.8). Of the factors contributing to the CVHI, glucose and total cholesterol scored best; diet least good. Average CVHIs for the population was 4.4 (SD ± 1.2) and 53% of the population had a good CV health. Determinants associated with good CV health were younger age, higher educational attainment, and HIV positivity. CVHIs showed good agreement with CIMT.Conclusion:CVHIs showed that more than half of the participants had a good CV health. Agreement between CVHIs and CIMT indicates potential use of CVHIs as a surrogate marker for CV risk. The study highlights the importance of education for health promotion; good CV health in HIV-positive participants may in part be attributed to more frequent health care contact and provision of chronic disease care.HighlightsGood cardiovascular health (CVH) was observed in 53% of the study population.In global comparison, rural African study participants showed a good CVH score.HIV positivity was associated with a good CVH score.CVH score showed good agreement with carotid intima-media thickness.

Risk factors during first 1,000 days of life for carotid intima-media thickness in infants, children, and adolescents: A systematic review with meta-analyses.

The first 1,000 days of life, i.e., from conception to age 2 years, could be a critical period for cardiovascular health. Increased carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis. We performed a systematic review with meta-analyses to assess (1) the relationship between exposures or interventions in the first 1,000 days of life and CIMT in infants, children, and adolescents; and (2) the CIMT measurement methods. Systematic searches of Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) were performed from inception to March 2019. Observational and interventional studies evaluating factors at the individual, familial, or environmental levels, for instance, size at birth, gestational age, breastfeeding, mode of conception, gestational diabetes, or smoking, were included. Quality was evaluated based on study methodological validity (adjusted Newcastle-Ottawa Scale if observational; Cochrane collaboration risk of bias tool if interventional) and CIMT measurement reliability. Estimates from bivariate or partial associations that were least adjusted for sex were used for pooling data across studies, when appropriate, using random-effects meta-analyses. The research protocol was published and registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42017075169). Of 6,221 reports screened, 50 full-text articles from 36 studies (34 observational, 2 interventional) totaling 7,977 participants (0 to 18 years at CIMT assessment) were retained. Children born small for gestational age had increased CIMT (16 studies, 2,570 participants, pooled standardized mean difference (SMD): 0.40 (95% confidence interval (CI): 0.15 to 0.64, p: 0.001), I2: 83%). When restricted to studies of higher quality of CIMT measurement, this relationship was stronger (3 studies, 461 participants, pooled SMD: 0.64 (95% CI: 0.09 to 1.19, p: 0.024), I2: 86%). Only 1 study evaluating small size for gestational age was rated as high quality for all methodological domains. Children conceived through assisted reproductive technologies (ART) (3 studies, 323 participants, pooled SMD: 0.78 (95% CI: -0.20 to 1.75, p: 0.120), I2: 94%) or exposed to maternal smoking during pregnancy (3 studies, 909 participants, pooled SMD: 0.12 (95% CI: -0.06 to 0.30, p: 0.205), I2: 0%) had increased CIMT, but the imprecision around the estimates was high. None of the studies evaluating these 2 factors was rated as high quality for all methodological domains. Two studies evaluating the effect of nutritional interventions starting at birth did not show an effect on CIMT. Only 12 (33%) studies were at higher quality across all domains of CIMT reliability. The degree of confidence in results is limited by the low number of high-quality studies, the relatively small sample sizes, and the high between-study heterogeneity. In our meta-analyses, we found several risk factors in the first 1,000 days of life that may be associated with increased CIMT during childhood. Small size for gestational age had the most consistent relationship with increased CIMT. The associations with conception through ART or with smoking during pregnancy were not statistically significant, with a high imprecision around the estimates. Due to the large uncertainty in effect sizes and the limited quality of CIMT measurements, further high-quality studies are needed to justify intervention for primordial prevention of cardiovascular disease (CVD).

Association between uric acid and atherosclerosis in community-dwelling older people: The SONIC study.

The association between serum uric acid (UA) and atherosclerosis in old people is controversial. Therefore, in this study, we clarified this association by assessing serum UA and common carotid atherosclerosis examined by carotid ultrasound in community-dwelling older people in their 70s, 80s and 90s in the SONIC study. A cross-sectional study was conducted involving 538 men and 577 women recruited from the community. The analysis was performed using serum UA as the explanatory variable and the maximum carotid intima-media thickness (max-CIMT) and mean-IMT as the dependent variables. The analysis was performed by multiple regression using traditional risk factors for atherosclerosis as adjustment variables. Analysis of the association between serum UA and IMT revealed a significant correlation only in women >70 years old. Max-CIMT (β = 0.081, 95% CI = 0.026, 0.136; P = 0.004) and mean-IMT (β = 0.015, 95% CI = 0.003, 0.029; P = 0.016) were significant. In the analysis of each age group, a significant correlation was only found in women in their 70s for mean-IMT (β = 0.031, 95% CI = 0.008, 0.053; P = 0.008). In community-dwelling women aged about 70 years old, elevated serum UA may be an independent risk factor for IMT thickening as a surrogate marker for atherosclerosis. Geriatr Gerontol Int 2021; 21: 94-101.

Cardio-ankle vascular index as an arterial stiffness marker improves on cardiovascular events by adding to framingham risk score

Abstract Background The cardio-ankle vascular index (CAVI) is a non-invasive measurement that evaluates arterial stiffness using the analysis of oscillometric waveform during cuff-Inflation. Several studies reported that CAVI is associated with cardiovascular risk factors, while the clinical prognostic value of CAVI as a surrogate marker of atherosclerosis has not been fully elucidated. Meanwhile, the Framingham risk score (FRS) is an established marker of cardiovascular outcomes. Purpose To investigate whether adding CAVI to Framingham risk score improves the prediction of cardiovascular events. Methods This prospective observational study included consecutive 422 patients with cardiovascular risk factors but without known coronary artery disease (69±8 years, 63% men). CAVI was measured by the oscillometric method with VaSera vascular screening system. Patients with atrial fibrillation, left ventricular ejection fraction &amp;lt;50%, both ABI&amp;lt;0.9, severe valvular diseases, or hemodialysis were excluded. Primacy outcomes were cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure and revascularization. Results During a median follow-up of 3.1 years, cardiovascular events occurred in 12.8% (3.3%, 15.7%, and 19.1% in the low, intermediate and high-risk group of stratification by FRS, respectively). The ROC curve analysis for discriminating cardiovascular events showed that the AUC of CAVI added to Framingham risk score was the highest compared to Framingham risk score and CAVI alone (CAVI added to Framingham risk score: AUC 66.9, 95% CI 59.6–74.2, Framingham risk score alone: AUC 61.5, 95% CI 53.8–69.1, CAVI alone: AUC 62.3, 95% CI 54.1–70.6). The logistic regression analysis demonstrated that CAVI and Framingham risk score were independent predictors of cardiovascular events (CAVI: OR 1.381, 95% CI 1.164–1.597, p=0.004, Framingham risk score: OR 1.135, 95% CI 1.044–1.225, p=0.007). Next, when logistic regression analysis was performed simultaneously on Framingham risk factor and CAVI, CAVI was an independent predictor of cardiovascular events (OR 1.347, 95% CI 1.124–1.569, p=0.009). Furthermore, in the likelihood ratio test, CAVI added to Framingham risk score significantly improved the cardiovascular event prediction ability than Framingham risk factor alone. Next, when patients with intermediate risk (n=217) were divided into two groups based on CAVI of 9.0, the Kaplan-Meier estimate showed that events occurred more frequently in higher CAVI group (9.3% and 29.1%, log-rank, P=0.009) and the C-statistic was 0.662. Multiple Cox analysis showed that, in the intermediate risk group, CAVI was an independent predictor of primary outcomes (HR 1.387 per 1 index, 95% CI 1.081–1.779, p=0.010). Conclusion The measurement of CAVI could be a useful predictor for cardiovascular events. In addition, the combination of CAVI and Framingham risk score could improve the predictability compared to the Framingham risk score alone. Funding Acknowledgement Type of funding source: None

Impact of sarcopenia on glycemic control and atherosclerosis in Japanese patients with type 2 diabetes: Cross-sectional study using outpatient clinical data.

This study examined the association among sarcopenia and various surrogate markers of atherosclerosis in Japanese patients with type 2 diabetes (T2D). Patients with T2D who visited the outpatient clinic comprised the study's participants. Handgrip strength (Grip), usual gait speed (GS) and skeletal muscle index, in addition to glycated hemoglobin, ankle-brachial index (ABI) and intima-media thickening (IMT), were measured in 1030 patients for the diagnosis of sarcopenia. From these results were obtained three categorical data (without sarcopenia [NS], sarcopenia with two factors [Sw2], sarcopenia with three factors [Sw3]), and continuous data for atherosclerosis. Glycated hemoglobin was significantly high among patients in the Sw3 category, as well as among all patients with sarcopenia, compared with those in the NS group, after adjustment was made for age, gender, duration of diabetes, and medications for hypertension and dyslipidemia. ABI was significantly low among the Sw2 and Sw3 patients, as well as among all patients with sarcopenia, but mean and maximum IMT were not when compared with the NS category of patients after the adjustment described above. However, skeletal muscle index, Grip and GS were positively associated with ABI after the adjustment. Grip and GS were negatively associated with maximum IMT after the adjustment. These results imply that measurements to diagnose sarcopenia could play an important role for early detection of preclinical atherosclerosis, specifically peripheral artery disease, among Japanese patients with T2D. Geriatr Gerontol Int 2020; 20: 1196-1201.

Impact of bariatric surgery on carotid intima-medial thickness and cardiovascular risk: results of a prospective study

The impact of bariatric surgery on atherosclerosis is a relatively less studied subject. Obesity has been identified as an independent risk factor for cardiovascular disease (CVD). Carotid intima-media thickness (CIMT), a surrogate marker for atherosclerosis and risk of CVD, has been found to be associated with obesity. Recent literature has shown that there is significant reduction in CIMT following bariatric surgery. The aim of this study was to evaluate the impact of bariatric surgery on CIMT and risk of CVD in an Indian population. This is a prospective study conducted in a tertiary referral centre in India. Patients undergoing bariatric surgery from December 2017 to September 2019 were included. CIMT measurements and American College of Cardiology/American Heart Association (ACC/AHA)-pooled cohort CVD risk scores were done before and at 6months and 12months after surgery. Fifty-four patients were enrolled, of which 70% were females. Mean age was 40.8 ± 10.7years. Mean pre-operative weight and mean BMI were 115.2 ± 21.9kg and 45.9 ± 6.5kg/m2, respectively. Patients who completed 12-month follow-up were considered for analysis of outcomes. There was significant reduction in BMI to 33.1 ± 5.7kg/m2 at 12months after surgery (p < 0.0001). Mean CIMT reduced significantly from 0.58 ± 0.08mm at baseline to 0.52 ± 0.10mm at 12months. Lipid profile, fasting blood sugar and HbA1C also improved, which resulted in reduction of lifetime and 10-year CVD risk from 42.3 to 26% and 4 to 1.5%, respectively, at 12months after surgery. Bariatric surgery results in significant reduction in CIMT and CVD risk in patients with morbid obesity.

Factors Associated with the Change in Carotid Maximum Intima-Media Thickness in Patients with Moderate-to-Advanced Stage Chronic Kidney Disease.

PurposeThe objective of this study was to determine factors associated with the change in carotid maximum intima-media thickness (IMT), an established surrogate marker of atherosclerosis, in moderate-to-advanced stage chronic kidney disease (CKD) patients.MethodsIn total, 130 moderate-to-advanced stage CKD patients (mean age: 67.6 ± 11.0 years old; 91 men and 39 women) were included in this retrospective, single-center, observational study. Relationships between the change in carotid maximum IMT and clinical and laboratory data were analyzed by using multivariate linear regression analyses.ResultsMean observation period was 2.9 ± 1.6 years. Mean carotid maximum IMT at baseline was 2.2 ± 1.0 mm, and the annual change in carotid maximum IMT was 0.06 ± 0.22 mm/year. Low-density lipoprotein (LDL)-cholesterol (β = 0.173, p < 0.05) and annual change in triglyceride (β = 0.175, p < 0.05) independently correlated with the annual change in carotid maximum IMT.ConclusionIncreases in LDL-cholesterol and triglyceride were associated with the rate of progression of carotid maximum IMT in moderate-to-advanced stage CKD patients.

Albuminuria and carotid intima-media thickness as surrogate markers of atherosclerosis in asymptomatic patients with type 2 diabetes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cerebral vasoreactivity, a surrogate marker of cerebrovascular disease, is not impaired in subjects with lifetime, untreated, congenital isolated GH deficiency.

Cerebrovascular disease (CeVD) is a major cause of death and disability. The role of the GH/IGF-I axis on CeVD risk is controversial. Patients with GH deficiency (GHD) in the setting of hypopituitarism often exhibit CeVD predisposing factors, like low nitric oxide generation, endothelial dysfunction, increased visceral fat mass, increased levels of LDL cholesterol, and increased intima-media thickness, a surrogate marker of atherosclerosis. However, several confounders such as the primary hypothalamic-pituitary lesion, hormonal replacement therapies, consequences of surgery and radiotherapy, may influence this relationship. Therefore, we decided to assess cerebral vasoreactivity, a surrogate marker of CeVD, in adult subjects with untreated isolated GHD (IGHD) due to the same homozygous null mutation in the GHRH receptor gene. A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, intima-media thickness measurement, and transcranial Doppler were performed. The intracranial hemodynamics (mean flow velocity, pulsatility and resistance indexes) were measured, and the response to the vasodilatory stimulus by breath-holding maneuver (breath-holding index) was calculated. IGHD and control groups were similar in Framingham risk score and intima-media thickness. Similarly, there was no difference in mean flow velocity, pulsatility, resistance, and breath-holding index. Lifetime, untreated IGHD does not cause impaired cerebral vasoreactivity.

Early life factors and their relevance to intima-media thickness of the common carotid artery in early adulthood.

Early life factors may predispose an offspring to cardiovascular disease in later life; relevance of these associations may extend to ‟healthy" people in Western populations. We examined the prospective associations between early life factors and adult carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, in a healthy German population. We studied term participants (n = 265) of the DONALD Study, with bilateral sonographic measurements of IMT (4-8 measurements on both left and right carotid artery) at age 18-40 years and prospectively collected data on early life factors (maternal and paternal age at child birth, birth weight, gestational weight gain and full breastfeeding (>17weeks). Mean IMT values were averaged from mean values of both sides. Associations between early life factors and adult IMT were analyzed using multivariable linear regression models with adjustment for potential confounders. Adult mean IMT was 0.56mm, SD 0.03, (range: 0.41 mm-0.78 mm). Maternal age at child birth was of relevance for adult IMT, which was sex specific: Advanced maternal age at child birth was associated with an increased adult IMT among female offspring only (β 0.03, SE 0.009 mm/decade, P = 0.003), this was not affected by adult waist circumference, BMI or blood pressure. Other early life factors were not relevant for IMT levels in males and females. This study suggests that advanced maternal age at child birth is of prospective relevance for adult IMT levels in a healthy German population and this association may be of adverse relevance for females only.

SAT-LB98 Early Atherosclerosis in Polycystic Ovary Syndrome. a Systematic Review, Meta-Analysis and Meta-Regression

Backgroung. Polycystic ovary syndrome (PCOS) is a common disorder affecting reproductive age women and is a cluster of endocrine and metabolic alterations ranging from impaired ovulation and androgen excess to abdominal obesity and metabolic syndrome leading to increased cardiovascular risk profile. Aim. To perform a meta-analysis on the effect of PCOS on surrogate markers of atherosclerosis, namely intima media thickness (IMT), flow-mediated dilation (FMD) and pulse wave velocity (PWV) and to run a meta-regression on the potential determinants of preclinical atherosclerosis. Methods. A search through Pubmed/Medline and ISI-web of knowledge retrieved 90 studies that were used for meta-analysis. Selected outcomes were IMT (n=6199), FMD (n=3090), and PWV (n=2477) while age, BMI, waist circumference, total testosterone, free androgen index (FAI), total-, HDL- and LDL-cholesterol, HOMA-index, systolic and diastolic blood pressure were used for meta-regression analysis. Results. Random effect meta-analysis showed that IMT was significantly increased (ES 0.47, 95% C.I. 0.64 to 0.30, p<0.0001), FMD was significantly impaired (ES -0.92, 95% C.I. -0.69 to -1.15, p<0.0001) and PWV was significantly increased (ES 0.28, 95% C.I. 0.48 to 0.08, p=0.006) in PCOS compared to controls. Meta-regression analysis showed that FMD was positively correlated with FAI (p=0.018) while negative correlations were found between Effect Size (IMT) and BMI (p=0.02), waist circumference (p=0.05) and total cholesterol (p=0.02). Conclusions. This meta-analysis shows a clear effect of PCOS on all markers of preclinical atherosclerosis (IMT, FMD and PWV). Heterogeneity of results is explained in part by the androgen status that was positively linked to impairment of FMD while increasing of anthropometric and metabolic variables (waist, BMI and total cholesterol) seem to overcome PCOS on preclinical atherosclerosis.

Differences in Carotid Intima-Media Thickness (CIMT) In Patients With Newly Diagnosed Hypertension, and Chronic Hypertensive Patients Treated by Calcium Channel Blockers (CCB) or Angiotensin Converting Enzyme (ACE)-Inhibitors

 Hypertension is a significant risk factor for cardiovascular diseases. It closely related to the inflammatory process and resulting in chronic inflammation, which had a critical role in the progression of atherosclerosis. Carotid Intima-Media Thickness (CIMT) was known as a surrogate marker of atherosclerosis. Anti-hypertensive drugs are expected to affect CIMT. Aim: to examine the difference CIMT between newly diagnosed hypertension and chronic hypertensive treated by ACE-I or CCB. Method: this cross-sectional study was conducted on 12 newly diagnosed hypertensive patients (control or group 1), 9 hypertensive patients treated by CCB (group 2), and 9 hypertensive patients treated by ACE-I (group 3). Their hypertensive condition was controlled at least for 6 months. We compared CIMT of patients and Tumour Necrosis Factor Alfa (TNF-α) also Interleukin-6 (IL-6) among the groups. Result: there was a significant difference in CIMT between the group 1 and 2 (0.86 vs 0.70; p = 0.027), group 1 and 3 (0.86 vs 0.69; p = 0.018). There was no significant difference between group 2 and 3 (0.70 vs 0.69; p = 0.88). There was no association between CIMT and TNF-α, IL-6, Low-Density Lipoprotein (LDL), triglycerides (TGs) levels, and body mass index (BMI), systolic blood pressure. Conclusion: we found that the CIMT of the control group was thicker than those of the treatment groups. Moreover, differences in the thickness of CIMT of the three groups were not associsted with level of TNF-α, IL-6, TG, and LDL, also BMI, and systolic blood pressure.

Study of risk factors and its correlation with constraint induced movement therapy for atherosclerosis in patients of coronary artery disease and their offspring

Background: A significant percent of cardiovascular event occurs without well-known modifiable risk. A new tool for early identification for atherosclerosis is required for early intervention. Aims and objectives of the study was to study the risk factors for CAD and its correlation with CIMT.Methods: One hundred and forty subjects were studied for the risk factors of CAD in Department of Medicine of G.R. Medical College, Gwalior from 2012 to 2013. Out of 140 subjects, 100 were patients having CAD and 40 age matched subjects were included as control group. Data was also recorded from their offspring. High resolution B mode ultrasonography was performed to assess CIMT of carotid arteries. The maximum CIMT of any one side of carotid artery was taken for study.Results: CAD was more prevalent among males (78%). Majority of the offspring of cases had age between 28-42 years and majority were male (73%). Most common risk factors for CAD was dyslipidemia (48%), hypertension (24%), diabetes (12%) and smoking (21%), whereas in offspring’s of CAD patients, dyslipidemia was seen in 28%, hypertension in 3%, diabetes and tobacco smoking in 12% and 24% respectively. The CIMT of CAD patients was significantly increased with increasing the number of risk factors and the same pattern was also seen in controls. The CIMT of asymptomatic offspring’s having positive family history was significantly more than the asymptomatic offspring without positive family history of CAD.Conclusions: CIMT measurements can be used as a surrogate marker of atherosclerosis as it has showed a direct link with number of risk factors of CAD.