Early Development Of Cardiovascular Disease Research Articles

The Association of Measures of the Micro- and Macro-Vasculature with Selenium and GPx Activity in a Young Bi-Ethnic Population: The African-PREDICT Study

Objective: Selenium plays an important physiological role as component for antioxidant selenoproteins such as glutathione peroxidase (GPx). Since oxidative stress contributes to hypertension development, it is likely that selenium deficiency may contribute to the burden of cardiovascular disease. To better understand the involvement of selenium and GPx in the early development of cardiovascular disease, we investigated in young, healthy black and white African men and women whether measures of the micro- and macrovasculature are related to selenium and GPx activity.Methods: In young adults (N = 394; aged 20–30 years) we determined serum selenium, GPx activity, microvascular measures (central retinal artery equivalent, central retinal vein equivalent, arteriolar-to-venular ratio [AVR], and estimated glomerular filtration rate [eGFR]), and macrovascular measures (pulse wave velocity, 24-hour pulse pressure [PP] and augmentation index [Aix]).Results: In multivariable-adjusted regression analyses, there were vasculoprotective associations between serum selenium and a microvascular measure (AVR [β = 0.23; p = 0.036]) in black African women and with a macrovascular measure (24-hour PP [β = −0.15; p = 0.048]) in white African women. In turn, GPx activity also showed a protective association with a microvascular measure (eGFR) in white African men (β = 0.23; p = 0.035), as well as with macrovascular measures (AIx, PP) in the black (β = −0.25; p = 0.027) and white African men (β = −0.22; p = 0.035), and black African women (β = −0.32; p = 0.001).Conclusions: Collectively the findings suggest a protective role for the micronutrient selenium and GPx on both the micro- and macrovasculature in a young, healthy bi-ethnic population.

Effects of Different Antihypertensive Drug Combinations on Blood Pressure and Arterial Stiffness.

Introduction:Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD).Aim:The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor.Methods:This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR).Results:SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027).Conclusion:These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.

Unhealthy Lifestyle and Nutritional Habits Are Risk Factors for Cardiovascular Diseases Regardless of Professed Religion in University Students.

To date, few studies have evaluated the possible association between religion and nutritional habits, lifestyle and cardiovascular risk in the university population. This study identified differences in the eating habits of Christian and Muslim university students and determined a possible association between the impact of religion on their lifestyles and the parameters related to cardiovascular risk. A cross-sectional study was performed with a sample population of 257 students (22.4 ± 4.76 year) at the campus of the University of Granada in Melilla (Spain). An anthropometric evaluation and a dietary assessment were performed. Blood pressure was also measured. There was a higher prevalence of overweight (29.1%) among Christian university students. The prevalence of pre-hypertension was similar between Christians and Muslims (48.3%) but was higher among Christian males (74.5%). Christian students presented higher levels of visceral fat. Students of both religions ingested carbohydrates, saturated fatty acids and total cholesterol, proteins, sodium and alcohol in excess. Significant positive correlations were found between food energy, sweets, snacks, soft drinks and body mass index (BMI) in both sexes and between the consumption of sausages-fatty meats and the systolic blood pressure (SBP) and body adiposity index (BAI) variables. Muslim students were less likely to consume alcohol (odds ratio [OR] = 7.88, 95% confidence interval [CI] = 4.27, 14.54). Christian and Muslim students presented improvable lifestyles and intake patterns. The high intake of saturated fatty acids, total cholesterol, sodium and alcohol in Christian students could lead to the early development of cardiovascular disease.

Association between preterm birth and the renin-angiotensin system in adolescence: influence of sex and obesity.

Preterm birth appears to contribute to early development of cardiovascular disease, but the mechanisms are unknown. Prematurity may result in programming events that alter the renin-angiotensin system. We hypothesized that prematurity is associated with lower angiotensin-(1-7) in adolescence and that sex and obesity modify this relationship. We quantified angiotensin II and angiotensin-(1-7) in the plasma and urine of 175 adolescents born preterm and 51 term-born controls. We used generalized linear models to estimate the association between prematurity and the peptides, controlling for confounding factors and stratifying by sex and overweight/obesity. Prematurity was associated with lower plasma angiotensin II (β: -5.2 pmol/l, 95% CI: -10.3 to -0.04) and angiotensin-(1-7) (-5.2 pmol/l, 95% CI: -8.4 to -2.0) but overall higher angiotensin II:angiotensin-(1-7) (3.0, 95% CI: 0.9-5.0). The preterm-term difference in plasma angiotensin-(1-7) was greater in women (-6.9 pmol/l, 95% CI: -10.7 to -3.1) and individuals with overweight/obesity (-8.0 pmol/l, 95% CI: -12.2 to -3.8). The preterm-term difference in angiotensin II:angiotensin-(1-7) was greater among those with overweight/obesity (4.4, 95% CI: 0.6-8.1). On multivariate analysis, prematurity was associated with lower urinary angiotensin II:angiotensin-(1-7) (-0.13, 95% CI: -0.26 to -0.003), especially among the overweight/obesity group (-0.38, 95% CI: -0.72 to -0.04). Circulating angiotensin-(1-7) was diminished whereas urinary angiotensin-(1-7) was increased relative to angiotensin II in adolescents born preterm, suggesting prematurity may increase the risk of cardiovascular disease by altering the renin-angiotensin system. Perinatal renin-angiotensin system programming was more pronounced in women and individuals with overweight/obesity, thus potentially augmenting their risk of developing early cardiovascular disease.

CLINICAL DATA AND HEMODYNAMIC PARAMETERS IN YOUNG ADULTS WITH ACUTE CORONARY SYNDROME

Aim.. To study the clinical and demographic data and hemodynamic parameters in patients with acute coronary syndrome (ACS) in young adults. Methods. 299 patients with ACS aged under 45 years admitted to the Department of Acute Myocardial Infarction (AMI) were enrolled in the study. The inclusion criteria were as follows: young adults under 45 years and the confirmed diagnosis of ACS. 53 healthy volunteers were included in the control group. Results. High risk of early developing ACS was established for young adults who were current smokers, had some form of dyslipidemia, overweight and suffered from arterial hypertension as well as those who had genetic predisposition to early development of cardiovascular disease. The most prevalent outcome of ACS was STEMI. 65.8% of patients underwent percutaneous coronary intervention (PCI). According to coronary angiography (CAG) findings, half patients had single-vessel coronary disease with predominant atherosclerotic lesions of the left anterior descending artery (LAD). Q-wave MI was commonly detected by routine ECG. 80% of patients had one hypokinetic segment. The study group commonly had anterior myocardial infarction. 12% of cases were complicated by left ventricular aneurysms. Conclusion. 299 young adults with ACS were admitted to the Altai Regional Cardiology Dispensary over 5 years. Most of patients had STEMI by routine ECG. Men suffered from ACS 6 times higher than women. This group of patients had the following traditional risk factors: smoking, arterial hypertension, overweight, and family history of cardiovascular disease. According to the CAG findings, half patients had single-vessel coronary disease, which was commonly associated with atherosclerotic lesion of the LAD. Few patients had atherosclerotic lesions of the right coronary artery and circumflex artery. Q-wave MI was commonly detected by routine ECG. 80% of patients had one hypokinetic segment.

Serum Cortisol and BMI in Chronic Diseases and Increased Early Cardiovascular Diseases

The purpose of this study was to examine the role of cortisol, and it is related to BMI in the chronic diseases which may increase early cardiovascular disease (CVD) in old Iraqi. The subjects were 116 adults, aged 51-71 years. Body Mass Index (BMI), Waist Circumferences (WC) and Waist Hip Ratio (WHR) were used as a measure of adiposity. Investigation showed highly significant difference between patients in BMI ranges, most of male were in an obese weight range (48.5%), as well in women. There were no significant correlations between serum cortisol concentration and age both gender groups. While there were highly significant correlations between cortisol level and BMI, waist, and WHR (except in female subjects), also there were highly significant correlations between cortisol level and SBP,DBP (mmHg)only in male. In both groups, total cholesterol concentration, FBS, and A1C were significantly correlated with serum cortisol. Negatively correlated has been observed between serum cortisol and HDL-C in men but not in women. In men, the results of cortisol with CV risk factors (dyslipidemia, D.M, hypertension, at least 2 risk factors and three risk factors) show significant differences (p>0.0). In summary, there is a major association between cortisol levels, obese, and chronic diseases. These conclusions promote the hypothesis that the opposing effect of adiposity on the chronic diseases might be mediated by cortisol. This association could cause early development of cardiovascular diseases even in males.

Serum Cortisol and BMI in Chronic Diseases and Increased Early Cardiovascular Diseases

The purpose of this study was to examine the role of cortisol, and it is related to BMI in the chronic diseases which may increase early cardiovascular disease (CVD) in old Iraqi. The subjects were 116 adults, aged 51-71 years. Body Mass Index (BMI), Waist Circumferences (WC) and Waist Hip Ratio (WHR) were used as a measure of adiposity. Investigation showed highly significant difference between patients in BMI ranges, most of male were in an obese weight range (48.5%), as well in women. There were no significant correlations between serum cortisol concentration and age both gender groups. While there were highly significant correlations between cortisol level and BMI, waist, and WHR (except in female subjects), also there were highly significant correlations between cortisol level and SBP,DBP (mmHg)only in male. In both groups, total cholesterol concentration, FBS, and A1C were significantly correlated with serum cortisol. Negatively correlated has been observed between serum cortisol and HDL-C in men but not in women. In men, the results of cortisol with CV risk factors (dyslipidemia, D.M, hypertension, at least 2 risk factors and three risk factors) show significant differences (p>0.0). In summary, there is a major association between cortisol levels, obese, and chronic diseases. These conclusions promote the hypothesis that the opposing effect of adiposity on the chronic diseases might be mediated by cortisol. This association could cause early development of cardiovascular diseases even in males.

Cardiovascular Disease Risk in Children and Adolescents

Atherosclerosis is a global health issue beginning in childhood. Children's early development of cardiovascular disease (CVD) risk factors may include exposure to key biological components responsible for vascular inflammation in young adults. A retrospective medical record review based on the 2008 American Academy of Pediatrics childhood lipid screening recommendations examined current and initial CVD risk factors for 227 at-risk school-aged children during wellness exams to better determine the age when children are most likely to convert from being risk-free to at risk for CVD. An original risk trend algorithm analyzed risk clustering and risk trend progression. Risk onset was young (M=2.88 years), with family risk most prevalent and risk clustering and accumulation noted, perhaps precluding primordial prevention.

Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo

Endothelial dysfunction is associated with early development of cardiovascular disease, making longitudinal measurements desirable. We devised a protocol using laser Doppler imaging (LDI) and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess the skin microcirculation longitudinally in mice every 4weeks for 24weeks in two groups of C57BL/6 mice, chow versus high-cholesterol diet(known to induce endothelial dysfunction). LDI measurements were compared with vascular function (isometric tension) measured using wire myography in the tail artery in response to ACh and SNP. Microvascular responses to ACh were significantly reduced in cholesterol-fed versus chow-fed mice from week 4 onwards (P<0.005, ANOVA). Pre-treatment with N(G)-nitro-l-arginine methyl-ester-hydrochloride (L-NAME) showed a significant reduction in ACh response compared with vehicle-treated animals (P<0.05) at baseline and at 12weeks. In cholesterol-fed mice, ACh responses were 226±21 and 180±21AU (P=0.03) before and after L-NAME, respectively. A reduction in ex-vivo ACh response was detected in the tail artery in cholesterol-fed mice, and a significant correlation found between peak microvascular ACh response and maximum ACh response in the tail artery (r=0.699, P=0.017). No changes were found in SNP responses in the microvasculature or tail artery. Using this protocol, we have shown longitudinal decreases in microvascular endothelial function to cholesterol feeding. L-NAME studies confirm that the reduced vasodilatation to ACh in cholesterol-fed mice was mediated partly through reduced NO bioavailability. Wire myography of tail arteries confirmed that in-vivo measurements of microvascular function reflect ex-vivo vascular function in other beds. Longitudinal assessments of skin microvascular function in mice could provide a useful translatable model for assessing early endothelial dysfunction.

Abstract P150: Aldosterone Dysregulation Increases Cardiovascular Risk in African-American Youth

Background: The prevalence of hypertension and blood pressure-related target organ damage in African-Americans is among the highest in the world. We hypothesize that this is in part due to aldosterone dysregulation among African-Americans beginning in youth and leading to the early development of cardiovascular disease in this population. To begin to test this hypothesis, we examined ethnic differences in aldosterone regulation in normal, healthy adolescents. Methods: The subjects in this study were 145 (60 Caucasian, 85 African-American) healthy, normotensive youth aged 15–19 years. Testing was performed following 72 hours on a controlled sodium diet. Testing consisted of the collection of aldosterone, systolic blood pressure (SBP), and urinary sodium excretion (U Na V) during continuous water intake (400 ml total) over a 2 hour period. An echocardiogram was also performed to measure target organ changes. Log transformations were performed on aldosterone levels prior to analyses. Results: African-American compared to Caucasian subjects had higher casual SBP (109±10 v 104±10; p=.006) and relative wall thickness (0.32±.03 v 0.34±.04; p=.003). During the testing procedure African-Americans also had lower levels of aldosterone (4.78±.6 v 4.35±.6 pg/ml; p =.001). In the Caucasian subjects only, aldosterone was inversely correlated with U Na V (r=−0.427; p=.001) and U Na V was positively correlated with SBP (r=0.356; p=.001). The subjects were divided into those in the upper and lower quartiles of salt intake for further analysis. The interaction between race and salt intake was significant for aldosterone (F=7.173; p=.008). Caucasian subjects with high salt intake had lower aldosterone (4.56±.59 v 5.02±0.59 pg/ml). However, aldosterone levels did not differ by salt intake in African-Americans. Summary and Conclusion: African-American subjects did not show the expected associations between aldosterone and the pressure natriuresis relation. Furthermore, African-Americans on the high salt intake failed to suppress aldosterone. These findings are consistent with our hypothesis that aldosterone dysregulation in youth may lead to the early development of cardiovascular disease in Africans-Americans.

Blood Pressure and Vascular Alterations with Growth in Childhood

The long preclinical phase of atherosclerosis involves the interaction of genetic and environmental factors that modulate the progression of disease from early life. A variety of noninvasive tests have been used to study the arterial phenotype of childhood, allowing identification of arterial alterations long before clinical symptoms of cardiovascular (CV) disease become apparent. These techniques have improved our understanding of the evolution of atherosclerosis, indentifying three major developmental factors which influence the future risk of CV disease in childhood: prenatal growth, early postnatal growth and childhood obesity. Specific changes in arterial properties and increased values of blood pressure are detectable in children with low birth weight, suggesting that intrauterine growth retardation could programme the future risk of CV disease. However, an accelerated growth rate in infancy and early childhood is often associated with low birth weight and with specific vascular alterations, making it difficult to distinguish the contribution of prenatal and postnatal growth patterns to later cardiovascular disease risk. Relationships between growth patterns and CV disease risk are further complicated by the link between rapid postnatal growth and later development of childhood overweight and obesity, conditions associated with early changes in vascular physiology and that potentially affect future CV outcome. This article aims to provide an overview of evidence in support of fetal programming and growth acceleration hypotheses for adult CV disease. Specific attention is given to obesity-related vascular alterations and their effects on future CV disease risk. We also summarise current non-invasive approaches to investigate the precursors and early development of CV disease, emphasising their potential applications in childhood.

Adiposity, fitness and metabolic risk in children: A cross-sectional and longitudinal study

To better understand the early development of cardiovascular disease, we examined the association of adiposity measures and cardiorespiratory fitness (CRF) with baseline values and changes in low-grade chronic inflammation and insulin resistance (IR) in school children. Eighty-three 1(st) and 5(th) grade children from a randomly selected control group of a physical activity intervention study (KISS) were prospectively studied during one academic year. Outcome variables included highly sensitive C-reactive protein (hs-CRP) and homeostasis assessment of IR (HOMA-IR). Adiposity measures included body mass index (BMI), waist circumference and the sum of skinfold thickness at four sites. CRF was assessed by the 20 m shuttle run test. All models were adjusted for age group, sex and pubertal group and included children who had a complete valid dataset for all variables. Baseline metabolic markers correlated positively with measures of adiposity and inversely with CRF (all p ≤ 0.02). On average, longitudinal changes in hs-CRP concentration increased with high baseline BMI in boys and skinfold thickness in both genders (both p < 0.01). Increases in adiposity had an additional effect on these changes (adjusted R(2) of the models including baseline and change in adiposity 0.49-0.53, p < 0.001). On the other hand, longitudinal changes in HOMA-IR were positively related to changes in BMI and waist circumference (p ≤ 0.03). Increases in HOMA-IR, but not in hs-CRP concentrations, were associated with low baseline CRF (p = 0.01). The relationship of baseline adiposity and CRF with increases in metabolic risk markers may have relevant implications for long-term cardiovascular risk. International Standard Randomised Controlled Trial Number (ISRCTN): isrctn.org 15360785.

Assessment of endothelial function by means of flow-mediated changes using pulse wave velocity.

Endothelial dysfunction is a leading cause of early development of cardiovascular diseases. Endothelial function can be assessed using ultrasound methods to watch the arterial flow-mediated dilation. It is also possible to find changes in pulse wave velocity (PWV) after induced ischemia related to the vessel diameter changes. Pre- and post-induced ischemia carotid-radial PWV was recorded in 226 hypertensive patients (150 women [63.5+/-12.4 years old] and 76 men [63.2+/-11.8 years old] and 55 healthy patients (38 women [63.1+/-12.6 years old] and 17 men [54.8+/-12.8 years old]). The authors considered normal endothelial function a PWV reduction of 5% from baseline. To assess nondependent endothelial dilation the authors performed carotid-radial PWV after sublingual administration of 5 mg of isosorbide dinitrate in a group of patients with abnormal flow-mediated dilation. A significant PWV reduction of 9.8% in normal patients and only 1.2% among hypertensive patients (P<.0005) was found. After sublingual isosorbide dinitrate intake the authors observed a greater fall in PWV (14%) than that observed in healthy people after induced ischemia. Carotid-radial PWV after induced ischemia decreased significantly in normal participants. No significant changes were observed in hypertensive patients. These results may offer a reliable tool to assess endothelial function in medium-size arteries.

Evaluation of Phytosterols in Milk and Yogurts Used as Functional Foods in Portugal

The early development of cardiovascular diseases, one of the major death causes in Europe, is clearly associated with high plasmatic cholesterol levels. However, it is demonstrated that the ingestion of phytosterols-enriched milk and yogurts could reduce cholesterolemia. The purpose of the present work was to assess the commercially available phytosterols-enriched milk and yogurts. As such, the available three milk and seven yogurt presentations in Portuguese market were collected during 2008 and analyzed through gas chromatography coupled with mass detection. All the analyzed milk samples were in agreement with the proportion established by the European Commission, with β-sitosterol as the more abundant phytosterol. However, and contrarily to milk, the different yogurt manufacturers had different options in the phytosterols added to the dairy foods commercialized.

Elevated Lp(a) with a small apo(a) isoform in children: risk factor for the development of premature coronary artery disease

levels of Lp(a) and low-molecular-weight apolipoprotein(a) isoform are strongly associated with the development of early cardiovascular disease. Certain types of apo(a) isoforms in combination with elevated levels of Lp(a) may be important in the determining of premature coronary artery disease. Therefore, we investigated the association of familial history of premature coronary artery disease and apo(a) size and Lp(a) levels in children and adolescents with hypercholesterolemia using a novel method determining apo(a) isoforms. Isoforms were classified in six phenotype patterns: S1-S4, B, F and according to their K-IV repeats. Apo(a) isoforms were divided into two groups: low-molecular- and high-molecular apo(a) isoforms. In subjects with double-banded apo(a) isoforms containing a small- and a large-isoform Lp(a) each contribution was based on the intensity of staining of the two bands. The percentage of patients with elevated levels of Lp(a) and a small apo(a) isoform (i.e. elevated small-isoform Lp(a)) was 46% in the risk group and 20% in the control group, p < 0.05. The percentage number of children and adolescents with elevated Lp(a) levels was higher in the risk group, reaching statistical significance (p < 0.05). Elevated levels of small-isoform Lp(a) might be a strong and independent risk factor for the development of premature coronary artery disease in children and adolescents with hypercholesterolemia.

Fat and Carbohydrate Metabolism during Submaximal Exercise in Children

During exercise, the contribution of fat and carbohydrate to energy expenditure is largely modulated by the intensity of exercise. Age, a short- or long-term diet enriched in carbohydrate or fat substrate stores, training and gender are other factors that have also been found to affect this balance. These factors have been extensively studied in adults from the perspective of improving performance in athletes, or from a health perspective in people with diseases. During the last decade, lifestyle changes associated with high-energy diets rich in lipid and reduced physical activity have contributed to the increase in childhood obesity. This lifestyle change has emerged as a serious health problem favouring the early development of cardiovascular diseases, insulin resistance or type 2 diabetes mellitus. Increasing physical activity levels in young people is important to increase energy expenditure and promote muscle oxidative capacity. Therefore, it is surprising that the regulation of balance between carbohydrate and lipid use during exercise has received much less attention in children than in adults. In this review, we have focused on the factors that affect carbohydrate and lipid metabolism during exercise and have identified areas that may be relevant in explaining the higher contribution of lipid to energy expenditure in children when compared with adults. Low muscle glycogen content is possibly associated with a low activity of glycolytic enzymes and high oxidative capacity, while lower levels of sympathoadrenal hormones are likely to favour lipid metabolism in children. Changes in energetic metabolism occurring during adolescence are also dependent on pubertal events with an increase in testosterone in boys and estrogen and progesterone in girls. The profound effects of ovarian hormones on carbohydrate and fat metabolism along with their effects on oxidative enzymes could explain that differences in substrate metabolism have not always been observed between girls and women. Finally, although the regulatory mechanisms of fat and carbohydrate balance during exercise are quite well identified, there are a lack of data specific to children and most of the evidences reported in this review were drawn from studies in adults. Isotope tracer techniques and nuclear magnetic resonance will allow non-invasive investigation of the metabolism of the different substrate sources in skeletal muscle.

Endothelial Function in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia

Adult survivors of childhood acute lymphoblastic leukemia (ALL) have an earlier than expected mortality from cardiovascular disease. This study examined endothelial function in 75 young (age 30.2+/-7.1 y) adult survivors of childhood ALL who received chemotherapy without cranial radiation (n=25) or chemotherapy combined with cranial radiation (n=50) compared with a healthy control group of similar sex, age, and weight (n=59). As part of a clinical follow-up study, endothelial-dependent flow-mediated dilation (FMD: % change in artery diameter after 5 min of occlusion) was assessed using high-resolution ultrasound of the brachial artery. Fifteen minutes after the measurement of FMD, sublingual nitroglycerin (0.4 mg) was administered and the brachial artery was imaged using ultrasound to assess endothelial-independent dilation (EID). All ultrasound imaging data were adjusted for baseline diameter. The healthy comparison group had a significantly greater FMD response (9.5%+/-2.9%) than both the chemotherapy only (6.5%+/-2.6%) and chemotherapy combined with radiation (7.1%+/-2.6%) groups. No statistical differences were observed in nitrate-mediated EID between the healthy comparison group (27.0%+/-5.0%) and the chemotherapy only (24.7%+/-6.7%) or chemotherapy combined with radiation (25.2%+/-7.1%) groups. Among the ALL survivors, female subjects had a significantly greater FMD and nitrate-mediated EID than male subjects even after correcting for baseline brachial artery diameter. These data suggest that young adults treated for ALL during childhood are at risk for impaired FMD regardless of whether or not they received cranial irradiation. The extent to which this mechanism relates to early development of cardiovascular disease in long-term childhood ALL survivors remains to be determined.

Serum Uric Acid and Target Organ Damage in Primary Hypertension

The role of serum uric acid as an independent risk factor for cardiovascular and renal morbidity is controversial. A better understanding of its relationship with preclinical organ damage may help clarify the mechanism(s) implicated in the development of early cardiovascular disease. We evaluated the association between uric acid and the presence and degree of target organ damage in 425 (265 males, 160 females) middle-aged, untreated patients with essential hypertension. Left ventricular mass index and carotid intima-media thickness were assessed by ultrasound scan. Albuminuria was measured as the albumin to creatinine ratio in 3 nonconsecutive first morning urine samples. Overall, patients with target organ damage had significantly higher levels of serum uric acid as compared with those without it (presence versus absence of left ventricular hypertrophy, P=0.04; carotid abnormalities, P<0.05; microalbuminuria, P<0.004; and at least 1 versus no organ damage, P<0.03). In women, the occurrence and severity of each target organ damage we examined increased progressively from the lower to the upper serum uric acid tertiles (P<0.01). After adjustment for body mass index, age, creatinine clearance, and high-density lipoprotein cholesterol, each standard deviation increase in serum uric acid entailed a 75% higher risk of having cardiac hypertrophy and a 2-times greater risk of having carotid abnormalities. These results support the role of serum uric acid as an independent, modifiable marker of cardiovascular damage.

Sub-Clinical Imflammation Contributes to the Early Development of Cardiovascular Disease in the Non-Hyperensive Young Healthy Prefessionals

Sub-Clinical Imflammation Contributes to the Early Development of Cardiovascular Disease in the Non-Hyperensive Young Healthy Prefessionals

Heterogeneous dynamic behaviour of intima media thickness along a short segment of the common carotid artery

Objective: It has been suggested that in early development of cardiovascular disease (CVD), arteries first become elastic and later they stiffen. Assessment of these locally changed structural and mechanical properties in a single subject non-invasively is difficult mainly due to the small spatial and temporal changes involved. Even at more advanced stages, changes in arterial wall properties are hard to determine because most methods suffer from low sensitivity and specificity. This study presents a new method, comparing spatial and temporal variances of structural and mechanical properties, thus allowing detection of spatial heterogeneities in a single subject, without the need of large subject group references.