Natural History of Carotid Atherosclerosis in Relation to the Hemodynamic Environment

Angiology ◽  
2016 ◽  
Vol 68 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Antonis I. Sakellarios ◽  
Paschalis Bizopoulos ◽  
Michail I. Papafaklis ◽  
Lambros Athanasiou ◽  
Themis Exarchos ◽  
...  
Keyword(s):  
Blood Flow ◽  
Natural History ◽  
Mass Transport ◽  
Carotid Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Three Dimensional ◽  
Density Lipoprotein ◽  
Magnetic Resonance Data ◽  
History Of ◽  
Plaque Growth

Carotid atherosclerosis may lead to devastating clinical outcomes such as stroke. Data on the value of local factors in predicting progression in carotid atherosclerosis are limited. Our aim was to investigate the association of local endothelial shear stress (ESS) and low-density lipoprotein (LDL) accumulation with the natural history of atherosclerotic disease using a series of 3 time points of human magnetic resonance data. Three-dimensional lumen/wall reconstruction was performed in 12 carotids, and blood flow and LDL mass transport modeling were performed. Our results showed that an increase in plaque thickness and a decrease in lumen size were associated with low ESS and high LDL accumulation in the arterial wall. Low ESS (odds ratio [OR]: 2.99; 95% confidence interval [CI]: 2.31-3.88; P < .001 vs higher ESS) and high LDL concentration (OR: 3.26; 95% CI: 2.44-4.36; P < .001 vs higher LDL concentration) were significantly associated with substantial local plaque growth. Low ESS and high LDL accumulation both presented a diagnostic accuracy of 67% for predicting plaque growth regions. Modeling of blood flow and LDL mass transport show promise in predicting progression of carotid atherosclerosis.

Have we learnt all from IMPROVE-IT? Part II. Subanalyses on the ef- fects of ezetimibe added to statin therapy on selected clinical and laborato- ry outcomes, cost effectiveness, guideline and clinical implications

2020 ◽  
Vol 18 ◽  
Author(s):  
Zlatko Fras ◽  
Dimitri P. Mikhailidis
Keyword(s):  
Statin Therapy ◽  
Artery Bypass ◽  
Low Density Lipoprotein ◽  
Bypass Graft ◽  
Density Lipoprotein ◽  
Drug Discontinuation ◽  
Atherosclerotic Cardiovascular Disease ◽  
History Of ◽  
Risk Cost ◽  
Cardiovascular Biomarkers

: In this second part of a review of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), we discuss the findings in relation to patients with stroke, the ACS phenotype, history of coronary artery bypass graft surgery, heart failure, concurrent polyvascular atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus, and different levels of expression of selected cardiovascular biomarkers. The combination therapy was proven safe, and drug discontinuation rates were not increased by adding ezetimibe. Since both statins and ezetimibe are now almost globally generically available, we can conclude that for secondary prevention of ASCVD, adding ezetimibe to high-intensity statin therapy further reduces low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk cost-effectively.

P193 CAROTID ATHEROSCLEROSIS, AORTIC STIFFNESS AND PENILE VASCULAR DAMAGE IN PATIENTS WITH ERECTILE DYSFUNCTION: RELATION TO LOW DENSITY LIPOPROTEIN LEVELS AND STATIN THERAPY

2017 ◽  
Vol 20 (C) ◽  
pp. 109
Author(s):  
Nikolaos Ioakeimidis ◽  
Charalambos Vlachopoulos ◽  
Athanasios Angelis ◽  
Dimitrios Terentes- Printzios ◽  
Christos Georgakopoulos ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Statin Therapy ◽  
Aortic Stiffness ◽  
Carotid Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vascular Damage ◽  
Low Density

Migraine in Children: Association With Primary and Familial Dyslipoproteinemias

PEDIATRICS ◽  
1986 ◽  
Vol 77 (3) ◽  
pp. 316-321
Author(s):  
Charles J. Glueck ◽  
Stephen R. Bates
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Degree Relative ◽  
Presumptive Diagnosis ◽  
History Of ◽  
Premature Myocardial Infarction ◽  
Disproportionate Number ◽  
Severe Migraine ◽  
Cerebral Vascular

We studied lipids and lipoprotein cholesterols in 39 children (26 boys, 13 girls) with severe migraine, to examine the hypothesis that primary and familial lipoprotein abnormalities might be associated with or predispose children to the migraine syndrome. Each of the children, 4 to 20 years of age, had severe migraine, leading to pediatric neurologic referral and therapy. Twenty-five of the 39 probands (64%) had a first degree relative with severe migraine, and 18% had a second degree relative with severe migraine. In 11 of the 39 kindreds (28%), there was a family history of premature myocardial infarction and/or cerebral vascular accident (&lt;age 55 years), involving one grandparent from each of ten kindreds and one parent in the 11th kindred. In nine of the 26 boys, low-density lipoprotein cholesterol (LDL-C) levels were greater than or equal to the age-, sex-, race-specific 90th percentile, and in three of these nine children, there was at least one additional first degree relative also having a primary top decile LDL-C level, consistent with the presumptive diagnosis of familial hypercholesterolemia. The finding of more than three times as many boys with migraine headache having top decile LDL-C than expected (9 v 2.6) was significant (x2 = 17.5, P &lt;.01). Also, there were six boys having bottom decile levels of high-density lipoprotein cholesterol (HDL-C); all six came from kindreds with at least one first degree relative also having bottom decile HDL-C. The finding of more than two times as many boys with migraine having bottom decile HDL-C than expected (6 v 2.6) was significant (x2 = 4.94, P &lt; .05). Of the 13 female pediatric probands, two had top decile LDL-C and two had bottom decile HDL-C and came from families with at least one additional first degree family relative also having a primary and similar dyslipoproteinemia. Our observations suggest that the clinical diagnosis of severe migraine in childhood should lead to measurement of lipids and lipoprotein cholesterols, particularly in boys, because they represent a cohort with a disproportionate number of hyper-β- and hypo-α-lipoproteinemic subjects. We speculate that primary and familial lipoprotein abnormalities, particularly those involving high levels of LDL-C and/or low levels of HDL-C, may be etiologically related to migraine, perhaps related to platelet hyperaggregability, and/or increased likelihood of cerebral vascular instability.

scholarly journals Sequence and Structure of Human Rhinoviruses Reveal the Basis of Receptor Discrimination

2003 ◽  
Vol 77 (12) ◽  
pp. 6923-6930 ◽  
Author(s):  
Marketa Vlasak ◽  
Soile Blomqvist ◽  
Tapani Hovi ◽  
Elizabeth Hewat ◽  
Dieter Blaas
Keyword(s):  
Low Density Lipoprotein ◽  
Three Dimensional ◽  
Density Lipoprotein ◽  
Major Group ◽  
Amino Acid Residues ◽  
X Ray ◽  
Vldl Receptor ◽  
Capsid Protein Vp1 ◽  
Three Dimensional Models ◽  
Positively Charged

ABSTRACT The sequences of the capsid protein VP1 of all minor receptor group human rhinoviruses were determined. A phylogenetic analysis revealed that minor group HRVs were not more related to each other than to the nine major group HRVs whose sequences are known. Examination of the surface exposed amino acid residues of HRV1A and HRV2, whose X-ray structures are available, and that of three-dimensional models computed for the remaining eight minor group HRVs indicated a pattern of positively charged residues within the region, which, in HRV2, was shown to be the binding site of the very-low-density lipoprotein (VLDL) receptor. A lysine in the HI loop of VP1 (K224 in HRV2) is strictly conserved within the minor group. It lies in the middle of the footprint of a single repeat of the VLDL receptor on HRV2. Major group virus serotypes exhibit mostly negative charges at the corresponding positions and do not bind the negatively charged VLDL receptor, presumably because of charge repulsion.

scholarly journals Improved scFv Anti-LOX-1 Binding Activity by Fusion with LOX-1-Binding Peptides

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Wei Hu ◽  
Qiuhong Xie ◽  
Hongyu Xiang
Keyword(s):  
Targeted Delivery ◽  
Structural Characteristics ◽  
Low Density Lipoprotein ◽  
Three Dimensional ◽  
Density Lipoprotein ◽  
Binding Activity ◽  
Single Chain ◽  
C Terminus ◽  
Density Lipoprotein Receptor ◽  
Therapeutic Molecules

The oxidized low-density lipoprotein receptor-1 (LOX-1) targeted single-chain variable fragment (scFvs) is a promising molecule for the targeted delivery of imaging and therapeutic molecules of atherosclerotic diseases; however, its applications are limited by the inherent low antigen affinity. In this study, the three-dimensional (3D) model of the anti-LOX-1 scFv was constructed and its docking with the LOX-1 protein was developed. To improve the LOX-1-binding activity, the anti-LOX-1 scFv was designed to fuse with one of three LOX-1-binding heptapeptides, LTPATAI, FQTPPQL, and LSIPPKA, at its N-terminus and C-terminus and in the linker region, which have different LOX-1-binding interfaces with the anti-LOX-1 scFv analyzed by an array of computational approaches. These scFv/peptide fusions were constructed, successfully expressed in Brevibacillus choshinensis hosts, and purified by a two-step column purification process. The antigen binding activity, structural characteristics, thermal stability, and stability in serum of these fusion proteins were examined. Results showed that the scFv with N-terminal fusing peptides proteins demonstrated increased LOX-1-binding activity without decrease in stability. These findings will help increase the application efficacy of LOX-1 targeting scFv in LOX-1-based therapy.

scholarly journals Patellar Maltracking Persists in Adolescent Females With Patellofemoral Pain

2017 ◽  
Vol 5 (2) ◽  
pp. 232596711668677 ◽  
Author(s):  
Victor R. Carlson ◽  
Barry P. Boden ◽  
Aricia Shen ◽  
Jennifer N. Jackson ◽  
Katharine E. Alter ◽  
...  
Keyword(s):  
Natural History ◽  
Pain Score ◽  
Three Dimensional ◽  
Patellofemoral Pain ◽  
Adolescent Females ◽  
Physical Activities ◽  
Symptom Improvement ◽  
Patellar Maltracking ◽  
History Of

Background: Patellofemoral pain is one of the most common conditions seen in sports medicine practices, particularly among adolescent females. However, the natural history of the underlying pathology in patellofemoral pain during puberty remains poorly understood. Purpose: The purpose of this longitudinal study is to assess changes in patellar maltracking patterns in subjects with patellofemoral pain as they mature from mid- to late adolescence. Study Design: Cohort study; Level of evidence, 3. Methods: Three-dimensional patellofemoral kinematic data were acquired during active knee extension-flexion using dynamic magnetic resonance imaging in 6 girls (10 knees; mean age, 14.0 years) with clinically diagnosed patellofemoral pain. The subjects then returned as late adolescents (mean age, 18.5 years) for follow-up scanning. Three-dimensional patellofemoral kinematic parameters were evaluated across the range of motion, but comparison between time points was restricted to 10° of flexion. Participation in impact and nonimpact physical activities, pain score based on the visual analog scale, and the anterior knee pain score were also compared across initial and follow-up visits. Results: All subjects reported improved patellofemoral pain symptoms at follow-up, and one subject reported complete resolution. However, relative to the initial visit, no differences were found in patellar maltracking. There was a decrease in hours engaged in impact physical activities for all subjects at follow-up. Conclusion: This study provides insight into the natural history of patellofemoral pain in adolescent females. The relatively unchanged patellofemoral maltracking across subjects suggests that potential anatomic and kinematic abnormalities contributing to patellofemoral pain during mid-adolescence persist during skeletal maturation. Symptom improvement for these subjects did not result from a change in patellofemoral tracking, but rather from other causes.

Lipid disorders in pregnancy

2021 ◽  
Vol 27 ◽  
Author(s):  
Anastasios Liberis ◽  
Stamatis Petousis ◽  
Panagiotis Tsikouras
Keyword(s):  
Pregnant Women ◽  
Low Density Lipoprotein ◽  
Safety Data ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Disorders ◽  
Severe Hypertriglyceridemia ◽  
History Of ◽  
Lipid Lowering Agents ◽  
In Pregnancy

: Dyslipidemia represents a major risk factor for cardiovascular disease. In addition, severe hypertriglyceridemia is an important cause of acute pancreatitis. Accordingly, the increase in serum lipid levels that are observed during pregnancy have potentially important implications. The management of dyslipidemia in pregnancy is further complicated by the lack of safety data during this period for most of the lipid-lowering agents. In the present review, we discuss the most important lipid disorders in pregnant women and their management. Pregnancy is characterized by increases in both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, which might result in severe complications both for the mother and the fetus. Accordingly, LDL-C and triglyceride levels should be monitored during pregnancy, particularly in women with a history of dyslipidemia. Diet is the mainstay of management of dyslipidemia in pregnant women and apheresis can also be considered in patients with homozygous familial hypercholesterolemia or severe hypertriglyceridemia. However, there is a pressing need for studies that with evaluate the safety of lipid-lowering agents during pregnancy.

Haemostatic, Endothelial and Lipoprotein Parameters and Blood Pressure Levels in Women with a History of Preeclampsia

1999 ◽  
Vol 81 (04) ◽  
pp. 538-542 ◽  
Author(s):  
Shu He ◽  
Angela Silveira ◽  
Anders Hamsten ◽  
Margareta Blombäck ◽  
Katarina Bremme
Keyword(s):  
Blood Pressure ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Normal Pregnancy ◽  
Index Pregnancy ◽  
History Of ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryTo determine whether perturbations of haemostatic function and lipoprotein metabolism prevail long after preeclampsia and increase the risk of future coronary heart disease (CHD), we conducted a follow-up study in women with (cases, n = 25) or without (controls, n = 24) a history of preeclampsia. Blood samples were taken in the follicular and in the luteal phases of a menstrual cycle. Levels of blood pressure (BP) and proteinuria measured during the index pregnancy were included in the evaluation. Compared to control women who had undergone a normal pregnancy, the formerly preeclamptic patients had higher systolic (p <0.01) and diastolic (p <0.05) BPs and increased plasma levels of von Willebrand factor (vWF), fibrinogen, cholesterol, triglycerides and very low density lipoprotein (VLDL) (all p <0.05). The lipid, vWF, and fibrinogen levels were positively related to the degree of BP elevation but not to the degree of proteinuria during the index pregnancy. Except for the increase in vWF level, all biochemical perturbations were only present in the luteal but not in the follicular phase samples. In conclusion, persistent endothelial dysfunction with ensuing dysregulation of blood pressure, haemostatic perturbation and dyslipoproteinemia after preeclampsia may indicate a proneness to future CHD.

scholarly journals The history of proprotein convertase subtilisin kexin-9 inhibitors and their role in the treatment of cardiovascular disease

2020 ◽  
Vol 11 ◽  
pp. 204062232092456
Author(s):  
Eun Ji Kim ◽  
Anthony S. Wierzbicki
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Lipid Lowering ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Activating Mutations ◽  
History Of ◽  
New Guidelines

A consensus has formed based on epidemiological studies and clinical trials that intervention to reduce low density lipoprotein cholesterol (LDL-C) will reduce cardiovascular disease (CVD) events. This has progressively reduced the thresholds for intervention and targets for treatment. Whist statins are sufficient for many people in primary prevention, they only partially achieve the newer targets of secondary prevention for established CVD. Increasing use of statins has highlighted that 1–2% cannot tolerate these drugs. Other cholesterol-lowering drugs such as ezetimibe add to the benefits of statins but have limited efficacy. The discovery of activating mutations in proprotein convertase subtilisin kexin-9 (PCSK9) as a cause of familial hypercholesterolaemia while inactivating mutations lower LDL-C led to the idea to develop PCSK9 inhibitors as drugs. This article reviews the history of lipid-lowering therapies, the discovery of PCSK9 and the development of PCSK9 inhibitors. It reviews the key trials of the current antibody-based drugs and how these have influenced new guidelines. It also reviews the controversy caused by their cost and the increasing application of health economics to determine the optimum strategy for implementation of novel therapeutic pathways and surveys other options for targeting PCSK9 as well as other LDL-C lowering compounds in late development.

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