Risk Factor For Atherogenesis Research Articles

Association between tissue human neutrophil peptide 1-3 levels and cardiovascular phenotype: a prospective, longitudinal cohort study.

ObjectiveInflammation is associated with atherogenesis. Although a higher neutrophil count is associated with the plaque burden, the role of neutrophil activation is unclear. Human neutrophil peptides 1–3 (HNP1–3) are a risk factor for atherogenesis in bench models and are elevated in human atheromas. This study aimed to examine the association between skin HNP1–3 deposition and the severity of coronary artery disease (CAD), including long-term outcomes.MethodsHNP1–3 levels were immunohistochemically quantified in skin biopsies, which were prospectively taken from 599 consecutive patients before clinically indicated coronary angiography. Established cardiovascular risk factors and blood markers for atheroinflammation were obtained. CAD severity and the incidence of repeat revascularization and mortality at 48 months of follow-up were assessed in relation to HNP1–3 levels.ResultsThe risk of CAD was independently associated with age and HNP1–3 in the entire cohort (F = 0.71 and F = 7.4, respectively). Additionally, HNP1–3 levels were significantly associated with myocardial necrosis (R = 0.26). At the follow-up, high HNP1–3 levels negatively affected mortality (19.54%) and recurrent revascularization (8.05%).ConclusionHNP1–3 tissue deposition is positively associated with the severity of CAD, myonecrosis, and long-term sequelae. HNP1–3 levels may be suppressed using colchicine.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in Ménière’s disease and vestibular neuritis

Objective several hypothesis including viral infection, vascular disturbance, and immune-mediated mechanisms have been proposed in Menière disease (MD) and vestibular neuritis (VN) and the role of inflammation has been also investigated. To evaluate the role of neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and metabolic parameters in MD and VN patients. Methods we retrospectively studied 120 subjects (40 affected by MD, 40 by VN and 40 normal controls). We analyzed glycaemia, Haematocrit Blood Test (HCT), leukocytes, neutrophils, lymphocytes, platelets, cholesterol, prothrombin time and the related international normalized ratio (PT-INR), fibrinogen, erythrocyte sedimentation rate (ESR), NLR and PLR. Results Neutrophils, leukocytes, cholesterol, ESR, NLR and PLR values of MD patients are significantly higher than normal controls. Higher significant values are reported for glycaemia, neutrophils, lymphocytes, leucocyte, fibrinogen, ESR, NLR and PLR in VN patients compared to NC. Conclusions High levels of NLR and PLR indicate the presence of an acute inflammatory state in both MD and VN. Our data confirm the role of proinflammatory state leading to microvascular injury together with risk factors for atherogenesis.

The influence of smoking on the functional state of microcirculation according to laser doppler flowmetry and clinical anamnestic data of patients with arterial hypertension

Background. Detailed study of the functional state of microcirculation in combination of arterial hypertension and tobacco smoking, as the most common and prognostically important risk factors for atherogenesis, will not only clarify pathogenetic effect of tobacco smoke on the terminal vascular bed, but also outline directions of active counteraction to it.Purpose. To study the effect of TS on the functional state of SM using laser Doppler flowmetry in patients with AH.Methods. 185 patients with stage 1,2 AH involved in the study were divided into 2 equivalent groups according to main clinical and laboratory data: group 1 – non-smokers (n = 134, mean age was 57.0 [50.0; 60.0]), group 2 – patients who smoke 1–1.5 packs of cigarettes per day (n = 51, mean age was 54.0 [48.0; 58.0]). Patients were prescribed short-acting antihypertensives drugs, which were used whenever required 5 days before the study. SM was investigated by laser Doppler flowmetry using occlusion test and amplitude-frequency spectrum analysis of hemoperfusion fluctuations.Results. Obtained data showed negative acute effect of ingredients of tobacco smoke on almost all structural elements of microhemocirculation. Revealed deviations are characterized by constriction of precapillary segment of microvascular bed with increase in myogenic tone and equal 3.1 units [2.6; 4.1] versus 2.3 units [1.7; 3.4] in the alternative group (p = 0.007), decrease in capillary blood flow from 4.5 units [3.5; 5.8] compared with the group of non-smokers – 5.2 units [4.0; 7.3] (p = 0.041), statistically significant intensification of arteriolar-venular blood flow with formation of venous congestion, limitation of dilated reserve of microcirculation.Conclusion. Tobacco smoking leads to significant microcirculation disorders that are projected onto changes in terminal vascular bed, inherent with AH, which significantly reduces the functional state of microcirculation, limits its reserve potential and promotes the development of tissue ischemia.

Порівняльна характеристика факторів атероґенезу в пацієнтів із симптомним і асимптомним перебігом атеросклеротичних каротидних стенозів

To study a comparative assessment of risk factors for atherogenesis in patients with different clinical manifestations of carotid atherosclerotic stenosis. The study included 106 patients (men — 74, women — 32) aged 39 to 79 years (mean age 62.6 ± 0.9), which devided to 3 clinical groups: Group I — 35 patients with acute atherothrombotic stroke with ipsilateral carotid stenosis, group II — 41 patients after acute cerebrovascular events and carotid endarterectomy, group III — 30 patients with asymptomatic atherosclerotic carotid stenosis and the control group, which consisted of 20 relatively healthy individuals. The degree of stenosis of the internal carotid arteries was highest (> 70 %) in the group of patients who underwent carotid endarterectomy. In addition in this group was prevalence younger men, compared with the group of asymptomatic stenosis and women (p = 0.00300), there was an older age of patients and moderate stenosis of 50–69 % (p = 0.00647). In patients with stenotic atherosclerosis of the internal carotid artery, there was a significant increase in the level of Lp-PLA2 compared with the control. This confirms that Lp-PLA2 can be considered as a marker of carotid atherosclerosis and influence the development of ischemic stroke. The highest level of Lp-PLA2 was observed in the clinical group of patients who underwent carotid endarterectomy after ischemic stroke and there was a tendency to a more significant increase in total cholesterol. This suggests a more aggressive course of the atherosclerotic process in patients in this group.

Microcirculation as a goal of correction in macroangiopathy (atherogenesis)

Background. The microcirculatory system (MCS) is a network of blood vessels that includes arterioles, capillaries, venules, and terminal lymphatic vessels. Microcirculation is characterized by the constant variability. Factors of atherogenesis development due to MCS dysfunction include shear stress, hyperglycemia, dyslipidemia, systemic and local inflammation, hypoxia and endothelial dysfunction mediated by oxidative stress. Laser Doppler flowmetry (LDF) is used to study microcirculation in the clinical settings. The advantages of LDF include simplicity, accessibility and non-invasiveness.
 Objective. To describe the features of microcirculation disorders and their elimination.
 Materials and methods. Analysis of literature data on this topic; own study. The study involved 98 patients (59 females; 39 males) with a mean age of 52.0 years. The first group consisted of patients with coronary heart disease (CHD) and chronic heart failure of I-IIA grades, the second – of relatively healthy individuals. All patients underwent LDF, ultrasound examination of the carotid arteries, and determination of anthropometric parameters.
 Results and discussion. MCS dysfunction is not only a risk factor for atherogenesis, but also a trigger for its acute complications (myocardial infarction, stroke, sudden death). Nitric oxide (NO) deficiency plays an important role in this. A potential target of therapeutic influence in the treatment of coronary heart disease is not only macrovascular system, but also vasa vasorum. The condition of the latter determines the course of atherosclerosis. According to the results of our own study, patients with CHD demonstrated a muscle mass decrease, an increase in waist and hip circumference, and in body mass index. In addition, the groups differed in thickness of the intima-media complex of both common carotid arteries (right common carotid artery: CHD group – 0.79±0.18 mm; group of relatively healthy individuals – 0.69±0.13 mm, p<0,05; left common carotid artery: CHD group – 0.81±0.19 mm, group of relatively healthy individuals – 0.70±0.14 mm, p<0,05). When assessing the indicators of wavelet analysis of LDF, a significant decrease in the rate of microcirculation and capillary blood flow reserve is revealed in the CHD group, as well as an increase in peripheral vascular resistance. According to previous own studies, sorbitol (Reosorbilact, “Yuria-Pharm”) and pentoxifylline (Latren, “Yuria-Pharm”) can be used to correct microcirculation disorders. The use of these drugs leads to vasodilation of precapillary sphincters and improvement of regional microperfusion.
 Conclusions. 1. Disorders of MCS are the pathogenetic factors of the atherogenesis. 2. Laser Doppler flowmetry is used to study microcirculation in the clinical settings. 3. In patients with CHD there is an increase in neuro- and myotonus of the MCS, which is associated with the impaired release of nitric oxide. 4. Changes in microcirculation contribute to the development of atherosclerosis, which should be taken into account when choosing treatment for such patients. 5. Sorbitol (Reosorbilact) and pentoxifylline (Latren) can be used to correct microcirculation disorders.

Circulating oxidized LDL, increased in patients with acute myocardial infarction, is accompanied by heavily modified HDL

Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(-)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(-) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues identified in apoB. The amount of oxPC adducts of apoB was higher in the LDL(-) than in the L1 fraction, as determined using Western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC mAb. The majority of PC species were not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.

Cardiovascular outcomes of Nephrotic syndrome in childhood (CVONS) study: a protocol for prospective cohort study

BackgroundNephrotic syndrome (NS) is characterized by dyslipidemia which is a well-known risk factor for atherogenesis. Atherosclerosis in childhood is mostly subclinical and endothelial dysfunction is known to precede this. Evidence for screening for endothelial dysfunction and cardiovascular risk factors and early identification of premature onset of atherosclerosis in childhood NS remains tenuous in the absence of well-designed prospective studies addressing cardiovascular comorbidity in NS. The objective of our study is to examine endothelial dysfunction and short-term cardiovascular outcomes in a carefully phenotyped cohort of patients with Nephrotic syndrome as compared to healthy controls.MethodsIn a multi-centric prospective cohort study, 70 Steroid Resistant NS (SRNS), 70 Steroid Sensitive (SSNS) patients along with 70 Healthy Controls are being recruited. After a baseline assessment of functional and structural status of heart (2D Echocardiography), arteries (Carotid Doppler and Intima Media Thickness measurements) and microcirculation [a combination of 2D Echocardiography, Laser Doppler Flowmetry (LDF) and Brachial Artery Flow mediated dilation (FMD) and Nail Fold Capillaroscopy (NFC)], the patients are being investigated for endothelial dysfunction. Venous blood sample (15 ml) is being collected for routine investigations and assay of biochemical endothelial markers through Flow Cytometry. The patients will be followed up at 12 months and 24 months after the recruitment to look for any change from baseline period.DiscussionThis study will able to provide a better understanding of the epidemiology of endothelial dysfunction and associated subclinical cardiovascular co-morbidity in childhood NS. Findings on characterization of prevalence of endothelial dysfunction and subclinical markers may be used to design future randomized controlled trials for evaluating the efficacy of preventive and therapeutic interventions in reducing the incidence of cardiovascular disease.

Infarkti mozga granične supratentorijalne lokalizacije i kardiovaskularni rizični faktori

Introduction: During the course and development of diverse cardiological diseases different central nervous system complications may develop. These are most frequently related to the nature of the cardiovascular entity itself. Aim: To evaluate the association between atherogenesis factors and border zones strokes within the cerebral medial artery vascularization territories. Methods: In total 30 patients were enrolled in the study. Stroke diagnosis was based according to clinical and neurological examination and brain CT findings. The study analyzed risk factors correspondingly to World Health Organization criteria. Results: In majority of patients (18; 60%) arterial hypertension was diagnosed. Additionally, following condition and risk factors were identified: cardiological diseases (17; 23.3%), cigarette smoking (13, 43.3%), hypercholeterolaemia (9; 30%) and diabetes (7; 23.3%). In the group with cardiological diseases most frequent was myocardial infarction (9; 56.2%), AV block II and III (5, 29.4%), atrial fibrillation with slow ventricular response (3; 17.6%). Conclusion: Results of the study point to conclusion that myocardial infarction, AV block II and III, atrial fibrillation with slow ventricular response, iatrogenic hypertension and traditional risk factors for atherogenesis significantly influences presentation of the border zone strokes within the cerebral medial artery vascularization territories.

Fasting Lipoprotein Lipase Protein Levels Can Predict a Postmeal Increment of Triglyceride Levels in Fasting Normohypertriglyceridemic Subjects.

Although a postprandial increment in triglyceride (TG) levels is considered to be a risk factor for atherogenesis, tests (e.g., fat load) to assess postprandial changes in TG levels cannot be easily applied to clinical practice. Therefore, fasting markers that predict postprandial TG states are needed to be developed. One current candidate is lipoprotein lipase (LPL) protein, a molecule that hydrides TGs. This study investigated whether fasting LPL levels could predict postprandial TG levels. A total of 17 subjects (11 men, 6 women, mean age 52 ± 11 years) with normotriglyceridemia during fasting underwent the meal test. Several fasting parameters, including LPL, were measured for the area under the curve of postprandial TGs (AUC-TG). The subjects' mean fasting TG level was 1.30 mmol/l, and their mean LPL level was 41.6 ng/ml. The subjects' TG levels increased after loading (they peaked after two postprandial hours). Stepwise multiple regression analysis demonstrated that fasting TG levels were a predictor of the AUC-TG. In addition, fasting LPL mass levels were found to be a predictor of the AUC-TG (β = 0.65, P < 0.01), and this relationship was independent of fasting TG levels. Fasting LPL levels may be useful to predict postprandial TG increment in this population.

ASSA14-13-01 Cigarette smoking-induced LDL dysfunction is partially reversible after smoking cessation

Background Increased level of low-density lipoprotein (LDL) is a well-established risk factor of atherogenesis. Cigarette smoking leads to endothelial dysfunction, an early event of atherogenesis. Objective To investigate the effect of smoking and smoking cessation on the atherogenesis of LDL and possible differences of this effect between long-term smokers with and without CAD Methods Human umbilical vascular endothelial cells (HUVECs) were treated with 50 and 100 μg/ml LDL isolated from long-term smokers with or without coronary artery disease (CAD), before and after smoking cessation. Functional changes of HUVECs were evaluated by measuring oxidative markers (MDA, LOX-1), NO, eNOS and inflammatory markers (TNF-α, IL-1β, MMP-9). Results PlasmaLDL levels of long-term (>10 years) smokers were significantly higher than that of non-smokers (p Conclusion Long-term cigarettes smoking had significant pro-oxidative and pro-inflammatory effects on LDLparticles which could lead to endothelial dysfunction. The detrimental effects of smoking on LDL could be partially reversed by 90days’ smoking cessation.

Lesiones orales como factores de riesgo de enfermedades sistémicas

Los problemas en la salud oral influyen en la condición general del individuo. El diagnóstico clínico de la enfermedad oral puede dar idea de la causa y el pronóstico, sin embargo no refleja directamente el nivel de alteración en el individuo. En algunas personas las enfermedades orales indican un factor de riesgo pero que no son de por vida, ni tan severos que deshabiliten sus capacidades, sin embargo sus consecuencias pueden impactar en la vida diaria en diferentes grados y provocar la percepción de incapacidad alterando el desenvolvimiento psicosocial. Diversos autores mencionan signos orales como factor de riesgo de enfermedades sistémicas. Patologias del canal radicular como lugar de brote de actinomicosis sistémica. Tambien se describe a la ulceración crónica del paladar duro donde se presenta el signo de tuberculosis pulmonar no diagnosticada, asi mismo la sífilis secundaria es inicialmente diagnosticada por lesiones orales. Otros autores sost ienen que el Sarcoma de Ewing primario envuelve al hueso de la cabeza y el cuello antes de repercutir sistemicamente. Tambien se describe que el Citomegalovirus en mucosal oral es una de las primeras manifestaciones del SIDA. Asi mismo se dice que la exposición hematógena a los estreptococos orales ha sido reconocido como potencial factor iniciador de la endocarditis bacteriana. La infección ha sido reconocida como factor de riesgo para la aterogénesis y los eventos trombóticos. Se encontró asociación significativa entre el componente periodontal del índice dental y la isquemia cerebrovascular. Hay lesiones orales que son factores de riesgo para desarrrollar una enfermedad sistémica. La osteodistrofia renal y los cambios en el tejido oseo son consecuencia de la insuficiencia renal. Los cambios en el hueso alveolar asociados a la osteodistrofia renal son similares a los hallados en el hiperparatiroidismo primario e incluyen pérdida generalizada de densidad ósea, adelgazamiento de la cortical de los huesos y pérdida total o parcial de la lámina dura.

Changes of serum parameters of TiO2 nanoparticle-induced atherosclerosis in mice

The evaluation of toxicological effects of nanoparticulate matter is increasingly important due to their growing occupational use and presence as compounds in consumer products. Numerous studies have shown that exposure to nanosized particles lead to systemic inflammation in experimental animals, but whether long-term exposure to nanosized particles induces atherogenesis is rarely evaluated. In the current study, mice were continuously exposed to TiO2 nanoparticles (NPs) at 1.25, 2.5, or 5mg/kg body weight, administered by nasal instillation for nine consecutive months, and the association between serum parameter changes and atherosclerosis in mice were investigated. The present findings suggested that chronic exposure to TiO2 NPs resulted in atherogenesis coupling with pulmonary inflammation, increased levels of serum triglycerides, glucose, total cholesterol, low-density lipoprotein cholesterol, advanced glycation end products, reactive oxygen species, NAD(P)H oxidases 4, C-reaction protein, E-selectin, endothelin-1, tissue factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and reduced levels of serum high-density lipoprotein cholesterol, nitric oxide and tissue plasminogen activator. Our study suggests an association of long-term exposure to TiO2 NPs with atherosclerosis and pulmonary inflammation. This finding demonstrates the hypothesized role of TiO2 NPs as a risk factor for atherogenesis.

Ferroportin is transcriptionally upregulated by oxldl through nrf2 and is counteracted by lps/ifng in murine macrophages

Objectives: Atherosclerosis is characterized by the formation of plaques in the vessel wall as a result of the accumulation and oxidation of LDL (oxLDL) and subsequent infiltration of immune cells. Infiltrated monocytes differentiate into macrophages which through oxLDL uptake develop into foam cells, a key feature in atherogenesis. Previous authors showed iron accumulation in atheroma plaques and proposed that iron might be a modifiable risk factor in atherogenesis. Recently, a new macrophage phenotype (Mox) was reported to result from macrophage exposure to oxidized phospholipids and to be Nrf2-dependent.

LDL fraction in rats‐fed trans fatty acids induces inflammatory factors in human umbilical vein endothelial cells (821.1)

Trans‐fatty acid is a well‐known risk factor of atherogenesis, however its mechanism has not been clarified. Plasmalogen is a subclass of phospholipids, characterized by vinyl‐ether bond in sn‐1 position, and known to have the anti‐atherogenenic property. We have found that trans‐fatty acids were incorporated into sn‐1 position of plasmalogen (trans‐type plasmalogen) in trans‐fatty acids fed rats. The aim of this study was to examine the physiological effects of trans‐type plasmalogen on vascular endothelium. Wistar‐ST male rats were fed an AIN‐93G based diet with or without 23% hydrogenated rape seed oil (including 40% trans‐fatty acids) for 8 weeks, and then we prepared LDL fraction from their aorta blood. Human Umbilical Vein Endothelial Cells (HUVEC, p=4~6) were cultivated until the cells were 80% confluent and the medium was changed containing rat LDL, then HUVEC were cultivated for 24h. The gene expressions of ICAM1, VCAM1 and MCP1 in HUVEC were increased in trans LDL group (LDL including trans‐type plasmalogen) more than control LDL group. MCP1 protein in cell supernatant was also higher in the trans group. These results suggest that LDL including trans‐type plasmalogen has inflammatory effects in HUVEC. We should clarify that trans‐type plasmalogens actually contribute the inflammatory effects in LDL on HUVEC.

Medroxyprogesterone Acetate Enhances Monocyte-Endothelial Interaction Under Flow Conditions by Stimulating the Expression of Cell Adhesion Molecules

Monocyte adhesion to endothelial cells is an important initial event in atherosclerosis and is partially mediated by adhesion molecule expression on the cell surface. Although estrogens inhibit atherosclerosis development, effects of coadministered progestogen remain controversial. We examined the effects of progestogen on cytokine-stimulated human umbilical venous endothelial cell (HUVEC) expression of adhesion molecules. In HUVECs, adhesion molecule mRNA levels were measured by real-time PCR. Protein expression was quantified by immunocytochemistry and ELISAs. To mimic the monocyte adherence to endothelial cells, we used a flow chamber system to assess progestogen effects on U937 monocytoid cell adherence to HUVEC monolayers. We also examined the suppression effects of adhesion molecules with small interference RNAs. mRNA levels of adhesion molecules in HUVECs treated with medroxyprogesterone acetate (MPA) or 17β-estradiol + MPA were 1.7- to 2.5-fold higher than those in the control. MPA increased the protein expression of E-selectin, P-selectin, and intercellular adhesion molecule-1 compared with that for the control (83.0 ± 0.7, 34.8 ± 1.2, and 5.4 ± 0.0 ng/mL, respectively), whereas other progestogens or 17β-estradiol additive to progestogens did not significantly change expression. MPA significantly increased U937 monocytoid cell adherence compared with the control (56.0 ± 1.5 vs 46.5 ± 3.5 adherent cells per 10 fields) but did not increase adherence to HUVECs with knocked down intercellular adhesion molecule-1. MPA increases cell adhesion molecule expression on HUVECs, causing increased numbers of monocytoid cells to adhere to HUVECs. These MPA effects may be a risk factor for atherogenesis on endothelial cells in postmenopausal women receiving hormone replacement therapy.

Early life Exposure to Environmental Tobacco Exposure and Atherogenesis

Background: Early exposure to environmental tobacco smoke (ETS) is associated with adverse health outcomes in children and adolescents: reduced lung function growth, asthma and adverse birth outcomes. Less is known on the impact of early life ETS exposure on cardiovascular health and atherosclerosis, although ETS is considered to be highly atherogenic in adults and remains a prevalent exposure in utero and childhood. Aim: 1. Present the state of knowledge on early life/childhood risk factors for atherogenesis, focusing on early life ETS exposure. 2. Present complexity and challenges in investigating early life origins of health and disease 3. and the SAPALDIA Youth Study designed to study early life factors of atherosclerosis. Results: Atherosclerosis is a multi-factorial disease with origins in childhood and in utero. Metabolic and morphologic alterations may result from ETS with toxic compounds crossing the placenta barrier and vaso-constrictive agents reducing the blood flow to the fetus. Childhood ETS exposure has been associated with cardiovascular risk factors: obesity,metabolic syndrome,leptin, adinopectin, CRP, oxidative stress. Studies on ETS and functional or structural changes of the vasculature in children are few. The challenge in research on early life origins of disease lies in the disparity of timing of exposure and disease manifestation. Developmental plasticity and adaptive responses of the human organism add to the complexity. The SAPALDIA Youth Study, the first Swiss offspring study, is designed to study early life factors and cardiovascular health, with a focus on atherosclerosis, addressing vulnerable time windows. Conclusion: ETS exposure in childhood is a risk factor for atherogenesis in adults and children. Considerable evidence supports the early life impact of ETS exposure on children’s cardiovascular risk profile. First findings pointing to functional and structural changes to the vasculature in children need affirmation. The SAPALDIA Youth Study can bridge the time windows of early exposure and later disease manifestation.

Association Between High-Normal Levels of Alanine Aminotransferase and Risk Factors for Atherogenesis

Liver disease has been associated with cardiovascular disorders, but little is known about the relationship between serum levels of alanine aminotransferase (ALT) and markers of atherogenesis. We investigated the relationship between low-normal and high-normal levels of ALT and an extended panel of cardiovascular risk factors among individuals with no known diseases in a primary care setting. We performed a retrospective analysis of data collected from 6442 asymptomatic patients at wellness visits to a primary care setting in central Virginia from 2010 through 2011. Serum levels of ALT were compared with levels of lipids and lipoproteins, as well as metabolic, inflammatory, and coagulation-related factors associated with risk for cardiovascular disease. Serum levels of ALT were higher than 40 IU/L in 12% of subjects, and in the high-normal range (19-40 IU/L in women and 31-40 IU/L in men) in 25% of subjects. ALT level was associated with the apolipoprotein B level, concentration and particle size of very-low-density lipoproteins, concentration of low-density lipoprotein (LDL) particles (LDL-P), and percentages of small dense LDL (sdLDL) and sdLDL-cholesterol (sdLDL-C) (P < .0001 for all). A high-normal level of ALT was associated with higher levels of LDL-C, LDL-P, sdLDL-C, and sdLDL particles (P < .001 for all). These effects were independent of age, body mass index, and hyperinsulinemia. Increasing levels of ALT and fasting hyperinsulinemia (>12 μU/mL) synergized with increasing levels of triglycerides, very-low-density lipoprotein particles, LDL-P, sdLDL-C, and percentage of sdLDL-C. Levels of APOA1, high-density lipoprotein-cholesterol, and high-density lipoprotein-class 2 were associated inversely with serum level of ALT (P < .0001 for all). In an analysis of asymptomatic individuals, increased serum levels of ALT (even high-normal levels) are associated with markers of cardiovascular disease.

Relation of Body Mass Index with Lipid Profile and Blood Pressure in Healthy Females of Lower Socioeconomic Group, In Kosi Region, Bihar.

Hypertension is an iceberg disease. It is the main risk factor for stroke and renal failure. Elevated levels of triglyceride, cholesterol and LDL-C are documented as risk factors for atherogenesis. LDL-C in its oxidized or acetylated form has been identified as a major atherogenic particle. Fifty four women between 20- 35 years of age attending Katihar medical college hospital OPD were used in this study. Their height, weight, systolic and diastolic blood pressures were recorded. Body Mass Index (BMI) was calculated by using their height (m2) and weight (kg). On the basis of BMI, all participants were divided into three groups that is under weight whose BMI was less than 19 kg/ m2, Normal who's BMI was between 19 and 26 kg / m2and overweight who's BMI was more than 26 kg / m2. The mean BMI of the three groups in the 54 participants was 150.1 mg/dl ±31.7, mean LDL-C was 91.6 mg/dl±22.6, mean HDL-C was 39.7 mg/dl ±9.1 and mean triglycerides were 93.9 mg/dl ±41.6. Mean systolic blood pressure was 114.1mmHg±11.8 and mean diastolic blood pressure was 74.1 mmHg ±7.9. There were significant differences in mean serum HDL-C, triglycerides, systolic and diastolic blood pressure among three BMI groups (P<0.05) but none in mean serum cholesterol and LDL-C. No significant correlation was found between any of the lipid profile variables and blood pressure variables with BMI. The importance of this finding is to enable care-givers in hypertension pay more attention to the control of obesity so that several complications associated with it might be prevented.

Parental history of premature coronary artery disease does not affect plasma levels of asymmetric dimethylarginine in young healthy adults

Family history of premature coronary artery disease (CAD) is a risk factor of atherogenesis and adverse coronary events. The aim of the study was to establish whether asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide formation, might be elevated in the asymptomatic offspring of patients with early‑onset CAD and whether it might contribute to subclinical atherosclerosis. We studied 20 healthy subjects (10 men and 10 women) aged from 19 to 30 years with a parental history of documented CAD before 60 years of age, and 20 controls with no evidence of parental CAD. ADMA and its isomer, symmetric dimethylarginine (SDMA), were determined by enzyme‑linked immunosorbent assays. Mean intima‑media thickness (IMT) of the common carotid arteries was assessed by B‑mode ultrasound. Characteristics of the 2 groups were similar, except for insignificant tendencies towards higher low‑density lipoprotein (LDL) cholesterol (P = 0.07) and estimated glomerular filtration rate (eGFR) (P = 0.06) in the group with a positive family history. Compared with controls, subjects with a parental history of premature CAD had increased IMT (0.54 ±0.05 vs. 0.48 ±0.05 mm; P <0.001) and similar levels of ADMA (0.66 ±0.17 vs. 0.74 ±0.15 μmol/l; P = 0.14) and SDMA (0.49 ±0.07 vs. 0.50 ±0.07 μmol/l; P = 0.61). The results did not change substantially on adjustment for LDL cholesterol and eGFR. In a multivariate analysis, parental CAD (P = 0.005) and LDL cholesterol (P = 0.06), but not ADMA, were independent positive IMT predictors. Our preliminary data suggest that elevated ADMA is not a part of the proatherogenic risk profile in the young adult offspring of patients with premature CAD.

Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis

The localization of atherosclerotic lesion formation to regions of disturbed blood flow associated with certain arterial geometries, in humans and experimental animals, suggests an important role for hemodynamic forces in the pathobiology of atherosclerosis. There is increasing evidence that the vascular endothelium, which is directly exposed to various fluid mechanical forces generated by pulsatile blood flow, can discriminate among these different biomechanical stimuli and transduce them into genetic regulatory programs that modulate endothelial function. In this brief review, we discuss how biomechanical stimuli generated by blood flow can influence endothelial functional phenotypes, and explore the working hypothesis of "atheroprone" hemodynamic environments as "local risk factors" in atherogenesis. In addition, we consider the therapeutic implications of the activation of "atheroprotective genes" and their role as "critical regulatory nodes" in vascular homeostasis.