Early Marker Of Cardiovascular Disease Research Articles

Investigating the cardio-protective abilities of supplemental L-arginine on parameters of endothelial function in a hypercholesterolemic animal model.

Endothelial dysfunction is now widely recognized as an early marker of cardiovascular disease, making its treatment, or complete avoidance, an emerging, interesting therapeutic target. This study investigated the ability of the highly intriguing amino acid L-arginine to influence endothelial function. Its therapeutic potential is also compared to that of known cardiovascular medications, namely nitroglycerin [a nitric oxide (NO) donor] and enalapril [an angiotensin-converting enzyme (ACE) inhibitor]. Fifty male New Zealand rabbits were included in the study, divided into 5 equal groups: control, hypercholesterolemia (untreated), hypercholesterolemia (+L-arginine), hypercholesterolemia (+enalapril), and hypercholesterolemia (+nitroglycerin). Biochemical investigations included measurement of circulating NOx, malondialdehyde (MDA), and lipid profile markers, as well as dimethylarginine dimethylaminohydrolase (DDAH) and ACE activities. Furthermore, aortic ACE activity and blood platelet aggregation were estimated. A histopathological examination and intimal thickness measurement were also conducted. Compared to the untreated hypercholesterolemic group, all agents were capable of positively influencing MDA levels, platelet aggregation and intimal thickness; however, only the L-arginine group was capable of beneficially and significantly altering both NOx levels and serum and aortic ACE activities. No agents were capable of modulating serum DDAH activity inhibited by hypercholesterolemia. Based on the results of this study, L-arginine appears to be a novel cardio-protective agent, illustrated by its ability to ameliorate the deleterious effects of hypercholesterolemia on endothelial function, in a manner comparable to, and sometimes more potent than, commonly used cardiovascular medications.

Chronic kidney disease and erectile dysfunction.

Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack.

A Novel Cardiac Bio-Marker: ST2: A Review

Cardiovascular diseases (CVD) are the major cause of death worldwide. The identification of markers able to detect the early stages of such diseases and/or their progression is fundamental in order to adopt the best actions in order to reduce the worsening of clinical condition. Brain natriuretic peptide (BNP) and NT-proBNP are the best known markers of heart failure (HF), while troponins ameliorated the diagnosis of acute and chronic coronary artery diseases. Nevertheless, many limitations reduce their accuracy. Physicians have tried to develop further detectable molecules in order to improve the detection of the early moments of CVD and prevent their development. Soluble ST2 (suppression of tumorigenicity 2) is a blood protein confirmed to act as a decoy receptor for interleukin-33. It seems to be markedly induced in mechanically overloaded cardiac myocytes. Thus, HF onset or worsening of a previous chronic HF status, myocardial infarct able to induce scars that make the myocardium unable to stretch well, etc, are all conditions that could be detected by measuring blood levels of soluble ST2. The aim of this review is to explore the possible role of ST2 derived-protein as an early marker of cardiovascular diseases, above all in heart failure and ischemic heart diseases.

Endothelial dysfunction in hyperandrogenic polycystic ovary syndrome is not explained by either obesity or ectopic fat deposition

PCOS (polycystic ovary syndrome) is associated with IR (insulin resistance), increased visceral fat and NAFLD (non-alcoholic fatty liver disease) all of which may contribute to endothelial dysfunction, an early marker of CVD (cardiovascular disease) risk. Our objective was to examine the relationships between endothelial dysfunction in PCOS, the volume of AT (adipose tissue) compartments and the size of intracellular TAG (triacylglycerol) pools in liver and skeletal muscle. A total of 19 women with PCOS (means±S.D.; 26±6years, 36±5kg/m2) and 16 control women (31±8years, 30±6kg/m2) were recruited. Endothelial function was assessed in the brachial artery using FMD (flow-mediated dilation). VAT (visceral AT) and abdominal SAT (subcutaneous AT) volume were determined by whole body MRI, and liver and skeletal muscle TAG by 1H-MRS (proton magnetic resonance spectroscopy). Cardiorespiratory fitness and HOMA-IR (homoeostasis model assessment of IR) were also determined. Differences between groups were analysed using independent Student's t tests and ANCOVA (analysis of co-variance). FMD was impaired in PCOS by 4.6% [95% CI (confidence interval), 3.0-7.7; P<0.001], and this difference decreased only slightly to 4.2% (95% CI, 2.4-6.1; P<0.001) when FMD was adjusted for individual differences in visceral and SAT and HOMA-IR. This magnitude of impairment was also similar in lean and obese PCOS women. The results suggest that endothelial dysfunction in PCOS is not explained by body fat distribution or volume. FMD might be a useful independent prognostic tool to assess CVD risk in this population.

Hypertension: The Link Between Erectile Dysfunction and Coronary Artery Disease

The ability to attain and then maintain an erection is the result of a dynamic balance between arterial inflow and cavernosal outflow. Any imbalance that either decreases arterial inflow and/or increases cavernosal outflow may result in symptomatic erectile dysfunction (ED). Current data suggest that vasculogenic ED is of arterial origin and primarily the result of the development of systemic endothelial dysfunction (EnD). Since systemic EnD is heralded as an early marker of cardiovascular disease, specifically coronary artery atherosclerotic heart disease (CAD), it has been suggested that the onset of ED can be used as a marker for either the presence, or future development, of CAD. However, the failure to find arterial dysfunction in some young men with largely vasculogenic ED, combined with the recognition that most men with ED, regardless of age, appear to have at least some cavernosal smooth muscle dysfunction, has prompted a reexamination of the roles of vascular endothelium and the cavernosal smooth muscle in the development of aging-related ED, as well as a reexamination of the significance of ED as a marker of subsequent cardiovascular disease. The unifying concept that explains all these events is the aging-related apoptosis that occurs within vascular smooth muscle. In the penis, this smooth muscle apoptosis will cause cavernosal veno-occlusive dysfunction (CVOD), which initially affects a man's refractory period. In the peripheral vascular system, the apoptotic process leads to an increase in peripheral vascular resistance, and patients may present with hypertension. Hypertension and CVOD, then, represent the same pathophysiologic disorder in two different organ systems.

Decreased heart rate variability in children born with low birth weight

Low birth weight (LBW) is associated with cardiovascular morbidity in adulthood. Imbalance in the autonomic nervous system (ANS) has been implicated as a mechanism behind the developmental programming of cardiovascular function. We hypothesized that deviations in the ANS function are seen in children born with LBW. Eighty-six children were included: 31 born preterm (<32 wk gestational age), 27 born at term but small for gestational age (SGA), and 28 born at term with normal birth weight (control). Twenty-four-hour Holter-electrocardiogram monitoring was performed at an average age of 9 y. Heart rate variability results were analyzed using frequency and time domain methods. All frequency components and both time domain parameters tested were significantly lower in the preterm and SGA children compared with controls. The low frequency/high frequency ratio was not significantly different between children born with LBW and controls. The autonomic control appears to be affected in children born with LBW despite gestational age at birth. Decreased total power, as an estimation of the ANS's global activity, rather than the balance between parasympathetic and sympathetic modulation might be an early marker of cardiovascular disease later on in life for LBW born children.

Erectile dysfunction in general medicine

Erectile dysfunction (ED) affects millions of men worldwide with implications that go far beyond sexual activity. ED is now recognised as an early marker of cardiovascular disease, diabetes mellitus (DM) and depression. The risk factors that are associated with ED (sedentary lifestyle, obesity, smoking, hypercholesterolaemia and the metabolic syndrome) are very similar to those for cardiovascular disease (CVD). Arguably, the awareness of ED as a symptomatic entity in the post-Viagra™ age is on the rise. Nevertheless, ED is commonly missed when evaluating patients in the hospital setting, either because of lack of consideration or awareness, or through simple embarrassment (of both clinician and patient). This article provides an overview of the aetiology, assessment and importance of ED and hopes to promote its consideration in day-to-day clinical practice.

Endothelial function measured using flow‐mediated dilation in polycystic ovary syndrome: a meta‐analysis of the observational studies

Women with polycystic ovary syndrome (PCOS) demonstrate an increased prevalence of cardiovascular disease (CVD) risk factors. Previous researchers have compared flow-mediated dilation (FMD), an early marker of CVD, in women with and without PCOS. Evidence for a PCOS-mediated reduction in FMD remains equivocal, potentially because of study differences in cohort-matching and measurement approaches. The aims of this systematic review and meta-analysis were to examine to what extent FMD is impaired in PCOS and to explore the influence of potential moderators of FMD reduction, such as age and BMI. A systematic review and meta-analysis of published observational studies comparing FMD in PCOS with control women. Twenty-one published studies were included (PCOS, n = 908; controls, n = 566). A subanalysis, using tighter inclusion criteria, involved seven studies (PCOS, n = 402; control, n = 251). Mean differences in FMD between PCOS and controls were synthesized. The subanalysis was delimited to the inclusion of age and BMI-matched controls. These factors were then explored as moderators using meta-regression. The pooled mean FMD was 3.4% (95% CI=1.9, 4.9) lower in PCOS compared with control women, with substantial heterogeneity between studies. In the subanalysis, the PCOS-mediated reduction in FMD was 4.1% (95% CI=2.7, 5.5). Heterogeneity remained substantial (I(2) =81%). Subsequent meta-regression indicated that the magnitude of FMD difference was not influenced by BMI (P = 0.17) nor age (P = 0.38). This systematic research synthesis indicates that endothelial function is compromised in PCOS women, even if they are young and nonobese.

Vitamin D status is associated with early markers of cardiovascular disease in prepubertal children

The associations of 25-hydroxyvitamin D [25(OH)D], non-high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL), and related markers of early cardiovascular disease (CVD) are unclear in prepubertal children. To investigate the association of 25(OH)D with markers of CVD. The hypothesis was that 25(OH)D would vary inversely with non-HDL-C. A prospective cross-sectional study of children (n=45; 26 males, 19 females) of mean age 8.3 ± 2.5 years to investigate the relationships between 25(OH)D and glucose, insulin, high-sensitivity C-reactive protein, and lipids. Vitamin D deficiency was defined as 25(OH)D <20 ng/mL; overweight as body mass index (BMI) ≥ 85 th but <95th percentile; and obesity as BMI >95th percentile. Twenty subjects (44.4%) had BMI <85%, and 25 had BMI of ≥ 85%. Eleven participants (24.4%) had 25(OH)D of <20 ng/mL, and 10 (22.2%) had 25(OH)D of >30 ng/mL. Patients with 25(OH)D of <20 ng/mL had significantly elevated non-HDL-C (136.08 ± 44.66 vs. 109.88 ± 28.25, p=0.025), total cholesterol (TC)/HDL ratio (3.89 ± 1.20 vs. 3.21 ± 0.83, p=0.042), and triglycerides (TG) (117.09 ± 71.27 vs. 73.39 ± 46.53, p=0.024), while those with 25(OH)D of >30 ng/mL had significantly lower non-HDL-C, TC/HDL, TG, and LDL (82.40 ± 18.03 vs. 105.15 ± 28.38, p=0.006). Multivariate analysis showed significant inverse correlations between 25(OH)D and non-HDL cholesterol (β=-0.337, p=0.043), and TC/HDL ratio (β=-0.339, p=0.028), and LDL (β=-0.359, p=0.016), after adjusting for age, race, sex, BMI, and seasonality. Vitamin D varied inversely with non-HDL, TC/HDL, and LDL. A 25(OH)D level of 30 ng/mL is associated with optimal cardioprotection in children.

Cardiovascular consequences of obesity: how will the UK cope?

“The UK has the second highest prevalence of obesity in the world, and something needs to be done about it.” These words were uttered by Sir Richard Thompson (President of the Royal College of Physicians [RCP]) in an introduction to a recent RCP working party report, Action on obesity: comprehensive care for all[1]. A key recommendation of the working party is that the healthcare system of the UK must adapt to the demands of an increasingly obese nation. Exactly how obese has the UK become? Using a definition of obesity based on the body mass index (BMI) (with levels of risk set by the National Institute for Health and Clinical Excellence [NICE], Table 1), data from the 2012 Health Survey for England show that, in 2010, 26% of men and women were obese, and that 42% of men and 32% of women were overweight. It is estimated that, by 2050, the majority of Britain’s population will be so categorised [2,3]. Perhaps of more concern is the observation that, in 2010, around 3-in-10 boys and girls (aged 2–15 years) were classified as overweight or obese (31% and 29%, respectively), which is very similar to the 2009 findings (31% for boys and 28% for girls). Table 1 Risk categories using the body mass index (BMI) set by the National Institute of Health and Clinical Excellence. Obesity has negative impacts in childhood as well as in the long term. In later life, affected children may experience adverse outcomes. These include: breathing difficulties; increased risk of fractures; hypertension; early markers of cardiovascular disease (CVD); insulin resistance (leading to type-2 diabetes mellitus [T2DM]); and psychological effects. The link between T2DM and obesity is evident particularly in children. In general, obese people are 80-times more likely to develop T2DM, and ≥75% of patients with DM die of cardiovascular causes, often prematurely [5]. Indeed, “overwhelming evidence supports the importance of obesity in the pathogenesis and progression of cardiovascular disease” [6]. Diseases of the heart (coronary heart disease, CHD) and circulatory system are the main cause of death in the UK, and accounted for 180,000 deaths in 2010 [7]. This represents just under 1-in-5 deaths in males and 1-in-10 in females. The incidence of CHD has declined by almost two-thirds among men in the UK over the last 25 years. More than half of this decline can be accounted for by favourable trends in the control of risk factors (e.g., reductions in blood pressure and smoking). It is disappointing, however, that this decline is being curbed by the increasing prevalence of overweight and obesity within the population, as shown in a 20-year follow-up of British men and women in the Whitehall II Study [8]. There is abundant evidence that the prevalence of CVD is highest in the lowest socioeconomic groups in the UK [7]. Similarly, there is an obvious north–south divide, whereby the prevalence of CHD death is highest for men and women in Scotland and lowest in England. This north–south divide is also apparent for obesity trends within the UK. For example, northern England has a higher prevalence of obesity than southern England [2]. Obesity has been stated to “stem from an energy imbalance derived from a complex interplay of behavioural, genetic, environmental, and social factors” [9]. Hence, to confront the social determinants of health, we must widen our perspective to intervene at many levels and, using cross-sectional ‘multi-pronged’ approaches, create social and physical environments that promote good health for all.

Arterial stiffness is increased in Hodgkin lymphoma survivors treated with radiotherapy

Radiotherapy has been associated with an increased risk for cardiovascular disease (CVD) in Hodgkin lymphoma survivors (HLS). Identifying subjects most likely to develop these complications is challenging. Arterial stiffness has been frequently used as an early marker of CVD, but has never previously been investigated in patients treated with radiotherapy. The carotid–femoral pulse wave velocity (PWV) and the distensibility coefficient (DC) of the common carotid artery were used as markers of arterial stiffness. Eighty-two HLS and 40 age- and gender-matched control subjects were studied. The aorta and the carotid arteries were situated within the radiation field in 50 and 39 patients. Mean PWV was not significantly different in HLS treated with radiotherapy on the mediastinum when compared to HLS treated without mediastinal radiotherapy and to controls. If HLS were 40 years or older at radiotherapy their PWV was significantly higher (8.54 m/s) than patients irradiated at a younger age (7.14 m/s, p = 0.004) and controls (6.91 m/s, p < 0.001), after adjusting for current age and other CVD risk factors. Mean DC was lower, indicative of stiffer arteries, in HLS treated with radiotherapy on the common carotid artery (2.79) than in HLS without radiotherapy (3.35, p = 0.029) and versus controls (3.60, p = 0.001). DC was lowest in HLS treated at 35 years of age or later (2.05), compared to HLS irradiated at a younger age (2.98, p = 0.046). In HLS, radiotherapy is associated with increased arterial stiffness. The effect of radiotherapy seems most evident when radiotherapy is administered at ages above 35–40 years.

Protocol for ADDITION-PRO: a longitudinal cohort study of the cardiovascular experience of individuals at high risk for diabetes recruited from Danish primary care

BackgroundScreening programmes for type 2 diabetes inevitably find more individuals at high risk for diabetes than people with undiagnosed prevalent disease. While well established guidelines for the treatment of diabetes exist, less is known about treatment or prevention strategies for individuals found at high risk following screening. In order to make better use of the opportunities for primary prevention of diabetes and its complications among this high risk group, it is important to quantify diabetes progression rates and to examine the development of early markers of cardiovascular disease and microvascular diabetic complications. We also require a better understanding of the mechanisms that underlie and drive early changes in cardiometabolic physiology. The ADDITION-PRO study was designed to address these issues among individuals at different levels of diabetes risk recruited from Danish primary care.Methods/DesignADDITION-PRO is a population-based, longitudinal cohort study of individuals at high risk for diabetes. 16,136 eligible individuals were identified at high risk following participation in a stepwise screening programme in Danish general practice between 2001 and 2006. All individuals with impaired glucose regulation at screening, those who developed diabetes following screening, and a random sub-sample of those at lower levels of diabetes risk were invited to attend a follow-up health assessment in 2009–2011 (n = 4,188), of whom 2,082 (50%) attended. The health assessment included detailed measurement of anthropometry, body composition, biochemistry, physical activity and cardiovascular risk factors including aortic stiffness and central blood pressure. All ADDITION-PRO participants are being followed for incident cardiovascular disease and death.DiscussionThe ADDITION-PRO study is designed to increase understanding of cardiovascular risk and its underlying mechanisms among individuals at high risk of diabetes. Key features of this study include (i) a carefully characterised cohort at different levels of diabetes risk; (ii) detailed measurement of cardiovascular and metabolic risk factors; (iii) objective measurement of physical activity behaviour; and (iv) long-term follow-up of hard clinical outcomes including mortality and cardiovascular disease. Results will inform policy recommendations concerning cardiovascular risk reduction and treatment among individuals at high risk for diabetes. The detailed phenotyping of this cohort will also allow a number of research questions concerning early changes in cardiometabolic physiology to be addressed.

Abstract 463: Cardiometabolic Risk Factors and Vitamin D 25OH levels in Puerto Rican Adolescents

Purpose: Overweight, obesity, hypertension (HTN), insulin resistance, and dyslipidemia have been recognized as cardiometabolic risk factors in adults. Early markers of cardiovascular disease in children are lacking. Low vitamin D (VITD) levels are associated with higher blood pressure, obesity and insulin resistance. We explored the association between traditional cardiometabolic risk factors and VITD levels with HTN status in adolescents. DESIGN METHODS: Cross-sectional pilot study in students from grades 9th - 12th in Puerto Rico. Fasting blood samples to estimate serum lipids, fasting glucose and vitamin D25OH levels were obtained, with anthropometric and blood pressure measurements. Variables described as mean [standard deviation (sd)] or frequencies and percentages as appropriate. Bivariate analysis using chi-square test; statistical significance was set at p&lt;0.05. Results: 78 adolescents, mean age: 16 years were studied. Mean BMI: 23.8 (range 17-39); 19.2% (15/78) were overweight and 16.7% (13/78) were obese. Pre-HTN observed in 7.7% (6/78), with 1 HTN. Hypercholesterolemia (≥170 mg/dl): 16.9% 13/77), low HDL levels (≤ 40 mg/dl): 67.5% 23/77), and hypertriglyceridemia (≥ 110 mg/dl): 15.6% (12/77). VITD levels were low (&lt; 30ng/dL) in 31% 24/77. Obese subjects were more likely to have insufficient VITD levels when compared with the non-obese, (61.5% vs 25%; p=0.02).At least 1 cardiometabolic risk factor was found in 69% (54/78); 33% (26/78) had 2 or more. Conclusion: Obesity is associated with low VITD levels and preHTN. Cardiometabolic risk factors are highly prevalent in our population. Interventions to prevent cardiovascular disease in Puerto Rican adolescents are required.

Cardiovascular Disease in Children with Chronic Kidney Disease

More than a decade ago, cardiovascular disease (CVD) was recognized as a major cause of death in children with advanced CKD. This observation has sparked the publication of multiple studies assessing cardiovascular risk, mechanisms of disease, and early markers of CVD in this population. Similar to adults, children with CKD have an extremely high prevalence of traditional and uremia-related CVD risk factors. Early markers of cardiomyopathy, such as left ventricular hypertrophy and dysfunction, and early markers of atherosclerosis, such as increased carotid artery intima-media thickness, carotid arterial wall stiffness, and coronary artery calcification, are frequently present in these children, especially those on maintenance dialysis. As a population without preexisting symptomatic cardiac disease, children with CKD potentially receive significant benefit from aggressive attempts to prevent and treat CVD. Early CKD, before needing dialysis, is the optimal time to both identify modifiable risk factors and intervene in an effort to avert future CVD. Slowing the progression of CKD, avoiding long-term dialysis and, if possible, conducting preemptive transplantation may represent the best strategies to decrease the risk of premature cardiac disease and death in children with CKD.

The effectiveness of web-based programs on the reduction of childhood obesity in school-aged children: A systematic review.

Review Objective The objective of this review is to synthesise the best available evidence on the effectiveness of web-based programs on the reduction of childhood obesity in school age children. Types of Participants This review will consider studies that include school age children regardless of gender, ethnicity, or national origin from 4-18 years of age. Types of Interventions This review will consider the use of web-based programs including, but not limited to the Internet, social networking media, Internet mobile applications, and email aimed at the reduction of obesity among school age children. Types of Outcomes The outcomes to be considered in this review include measures of overweight and obesity among school aged children as measured by valid and reliable measurements including but not limited BMI, body weight, and/or waist circumference.

Erectile dysfunction and hypertension: impact on cardiovascular risk and treatment.

Erectile dysfunction (ED) is a common complaint in hypertensive men and can represent a systemic vascular disease, an adverse effect of antihypertensive medication or a frequent concern that may impair drug compliance. ED has been considered an early marker of cardiovascular disease. The connection between both conditions seems to be located in the endothelium, which may become unable to generate the necessary dilatation in penile vascular bed in response to sexual excitement, producing persistent impairment in erection. On the other hand, the real influence of antihypertensive drugs in erectile function still deserves discussion. Therefore, regardless of ED mechanism in hypertension, early diagnosis and correct approach of sexual life represent an important step of cardiovascular evaluation which certainly contributes for a better choice of hypertension treatment, preventing some complications and restoring the quality of life.

Glucose intolerance: is it a risk factor for cardiovascular disease in children with chronic kidney disease?

A total of 66 children and adolescents with chronic kidney disease (CKD) (20 pre-dialysis patients and 46 chronic dialysis patients) were evaluated to address the prevalence of abnormalities in glucose and insulin metabolism and their association with cardiovascular disease. Glucose intolerance was assessed using an oral glucose tolerance test; insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). Carotid artery intima-media thickness (IMT) and left ventricular hypertrophy (LVH) were examined as early markers of cardiovascular disease. Thirty-four patients (7 pre-dialysis, 27 dialysis) exhibited an abnormal glucose tolerance; however, ten patients (7 pre-dialysis, 3 dialysis) were insulin-resistant. Height-specific standard deviation scores of carotid artery IMT were above normal in three of the pre-dialysis patients (15%) and in 34 of the dialysis patients (74%). LVH was present in seven pre-dialysis (35%) and 34 dialysis patients (74%). In addition, two of the pre-dialysis patients (10%) and 18 of the dialysis patients (39%) had severe LVH. The prevalence of both increased carotid artery IMT and LVH were similar in patients with or without glucose intolerance in both groups, but severe LVH was more prevalent in pre-dialysis patients with glucose intolerance (p = 0.042). The multivariate analyses showed that neither carotid artery IMT nor LVM index was predicted by serum glucose levels or HOMA-IR. In conclusion, children with CKD are at a high risk of glucose intolerance and also have a greater risk of subclinical cardiovascular disease (CVD). However, the presence of glucose intolerance does not appear to be an independent risk factor for increased carotid artery IMT or LVH.

Racial differences in arterial stiffness among adolescents and young adults with type 2 diabetes.

African-American adults demonstrate a higher prevalence of cardiovascular complications including myocardial infarction and stroke. Whether similar racial disparities are present to suggest African-Americans adolescents are at higher risk to develop cardiovascular disease is not known. Thus, we compared arterial stiffness, an early marker of cardiovascular disease, in African-American and Caucasian adolescents and young adults with type 2 diabetes. Demographic, anthropometric, laboratory data, and arterial stiffness measures including pulse wave velocity (PWV) and augmentation index (AIx) were collected in a cross-sectional study of 215 adolescents (average age 18 yr) with type 2 diabetes (55% African-American and 65% female). Compared to Caucasians, African-Americans had increased PWV (6.21 ± 0.87 vs. 6.96 ± 1.30, p < .01) and AIx (4.44 ± 11.17 vs. 7.64 ± 12.02, p = 0.05). Regression modeling demonstrated age, lipids, blood pressure, and duration of diabetes were differently associated with arterial stiffness in each race group (p < 0.05). African-American adolescents and young adults with type 2 diabetes have increased vascular stiffness than age-matched Caucasians. This process is mediated by different cardiovascular risk factors. These results suggest race-specific risk factor modification may be helpful to prevent early cardiovascular disease in this high risk population.

Circulating Oxidized LDL and Inflammation in Extreme Pediatric Obesity

Oxidative stress and inflammation have not been well-characterized in extreme pediatric obesity. We compared levels of circulating oxidized low-density lipoprotein (oxLDL), C-reactive protein (CRP), and interleukin-6 (IL-6) in extremely obese (EO) children to normal weight (NW) and overweight/obese (OW/OB) children. OxLDL, CRP, IL-6, BMI, blood pressure, and fasting glucose, insulin, and lipids were obtained in 225 children and adolescents (age 13.5 ± 2.5 years; boys 55%). Participants were classified into three groups based on gender- and age-specific BMI percentile: NW (<85th, n = 127), OW/OB (85th- <1.2 times the 95th percentile, n = 64) and EO (≥1.2 times the 95th percentile or BMI ≥35 kg/m(2), n = 34). Measures were compared across groups using analysis of covariance, adjusted for gender, age, and race. Blood pressure, insulin, and lipids worsened across BMI groups (all P < 0.0001). OxLDL (NW: 40.8 ± 9.0 U/l, OW/OB: 45.7 ± 12.1 U/l, EO: 63.5 ± 13.8 U/l) and CRP (NW: 0.5 ± 1.0 mg/l, OW/OB: 1.4 ± 2.9 mg/l, EO: 5.6 ± 4.9 mg/l) increased significantly across BMI groups (all groups differed with P < 0.01). IL-6 was significantly higher in EO (2.0 ± 0.9 pg/ml) compared to OW/OB (1.3 ± 1.2 pg/ml, P < 0.001) and NW (1.1 ± 1.0 pg/ml, P < 0.0001) but was not different between NW and OW/OB. Extreme pediatric obesity, compared to milder forms of adiposity and NW, is associated with higher levels of oxidative stress and inflammation, suggesting that markers of early cardiovascular disease and type 2 diabetes mellitus are already present in this young population.

Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease

IntroductionAdvanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are increased in patients with long-standing RA and whether AGE accumulation is related to disease activity, disease severity and measures of (premature) atherosclerosis, such as endothelial activation, endothelial dysfunction and intima media thickness (IMT).MethodsIn a cross-sectional study, 49 consecutive RA patients with longstanding disease (median disease duration of 12.3 years (range 9.3 to 15.1)), receiving standard of care, were included and compared with 49 age- and sex-matched healthy controls (HC). AGEs were determined by skin autofluorescence. Disease activity was evaluated by the Disease Activity Score of 28 joints (DAS-28) score and joint damage by modified Sharp-v.d. Heijde score. Endothelial activation (soluble vascular cellular adhesion molecule-1) sVCAM-1, von Willebrand factor (vWF), thrombomodulin), endothelial dysfunction (determined by small artery elasticity (SAE)) and IMT were measured and related to AGE accumulation.ResultsAGEs were increased in RA patients (median 2.4 arbitrary units (a.u.), range 1.6 to 4.2) compared to HC (2.2, 1.3 to 3.8). RA patients had a DAS-28 score of 2.9 (0.8 to 6.9) and a modified Sharp-v.d. Heijde score of 19 (0 to 103). sVCAM-1 and vWF levels were higher in RA patients. SAE was significantly decreased in RA (3.9 ml/mmHg (1.4 to 12.2) vs. 6.1 in HC (1.7 to 12.9). IMT did not differ between the two groups. Combining both groups' AGEs correlated with vWF, sVCAM-1 and IMT, and was inversely related to SAE. In RA, AGEs had an inverse relation with SAE, but did not relate to disease activity or radiological damage. In multivariate analysis for both groups, smoking, glucose levels, vWF, SAE and male gender were significantly related to the formation of AGEs.ConclusionsAGEs were increased in RA patients with long-standing disease and without signs of premature atherosclerosis. AGEs were related to endothelial activation and endothelial dysfunction. This supports the hypothesis that in RA AGEs may be an early marker of cardiovascular disease.