Abstract 20310: Cardiovascular Risk Markers in a Large Cohort of Children With Genetically Verified FH Show No Inheritance-Related but LDL Receptor Mutation-Type and Family History of CVD-related Variance

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ingunn Narverud ◽  
Jeaninen R van Lennep ◽  
Jacob J Christensen ◽  
Jorie Versmissen ◽  
Jon M Gran ◽  
...  
Keyword(s):  
Family History ◽  
Mixed Model ◽  
Ldl Cholesterol ◽  
Plasma Lipids ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Premature Cardiovascular Disease ◽  
History Of ◽  
The Impact

Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused primarily by mutations in the low density lipoprotein (LDL) receptor gene. FH patients have increased total- and LDL cholesterol leading to accelerated atherosclerosis and premature cardiovascular disease (CVD). In an FH pregnancy the absolute rise in lipid levels are often much higher than in healthy pregnancies, and this maternal hypercholesterolemia may thus contribute to an unfavorable in utero environment potentially increasing susceptibility of adult CVD. Few studies have investigated whether maternal FH is associated with an unfavorable phenotype in offspring compared with paternal FH inheritance. Hypothesis: The aim of the present study was to investigate the impact of maternal vs. paternal FH on pre-treated plasma lipids. In addition, the effect of LDL receptor mutation types and Family history of early CVD in FH children was evaluated Methods: We included 1063 children with FH (0-19 years) in the study. Five-hundred had inherited FH maternally and 563 paternally. Furthermore, 624 children with FH had an LDL receptor negative mutation and 332 of the FH children had an FH grandparent suffering from early CVD whereas the remaining children had an FH grandparent with late or no CVD. Differences were tested for using a random intercept mixed model taking account for between-family variation. Results: Children with maternal FH did not have different levels of total-, LDL- or HDL-cholesterol, triglycerides, apoA1, apoB, lipoprotein (a) compared with children With paternal FH. Moreover, children with LDL receptor negative mutations had higher levels of total- and LDL cholesterol in addition to apoB, and concomitantly lower levels of HDL-cholesterol and apoA-1 than children with other LDL receptor mutations. Finally, children with an FH grandparent with early CVD had significant higher LDL-cholesterol levels than children without. Conclusions: Maternal FH does not lead to a more unfavorable phenotype in untreated FH children. However, both FH children with LDL receptor negative mutation and FH children with early CVD in family had a more unfavorably phenotype. Hence statin treatment should potentially be initialized earlier in this group.

scholarly journals Familial Hypercholesterolemia: Three “under” (Understood, Underdiagnosed, and Undertreated) Disease

2021 ◽  
Author(s):  
Vladimir O. Konstantinov
Keyword(s):  
Familial Hypercholesterolemia ◽  
Time Course ◽  
Ldl Cholesterol ◽  
Genetic Disorders ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Blood Cholesterol ◽  
Healthy Population ◽  
Loss Of Function

Familial hypercholesterolemia (FH) is one of the most prevalent genetic disorders leading to premature atherosclerosis and coronary heart disease. The main cause of FH is a mutation in the LDL-receptor gene that leads to loss of function of these receptors causing high levels of blood cholesterol. The diagnosis of FH is not very easy. Wide screenings are needed to reveal high levels of LDL cholesterol among “healthy” population. If the patient has MI or stroke at an early age, high levels of LDL cholesterol, and tendon xanthomas, the diagnosis of FH becomes much more clear. Genetic testing is a gold standard in the diagnosis of FH. There are several factors, influencing the time course of FH. Smoking males with low levels of HDL cholesterol have an extremely higher risk of death than nonsmoking females with high HDL cholesterol. Management of FH includes low cholesterol diet, statin and ezetimibe treatment, PCSK inhibitors, and LDL aphaeresis. Early and effective treatment influences much the prognosis in FH patients.

Cholesterol Screening?

PEDIATRICS ◽  
1990 ◽  
Vol 85 (6) ◽  
pp. 1125-1126
Author(s):  
BARBARA A. DENNISON
Keyword(s):  
Family History ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Screening Strategy ◽  
The Third ◽  
The Past ◽  
Cholesterol Screening ◽  
Premature Cardiovascular Disease ◽  
History Of

To the Editor.— The paper by Drs Garcia and Moodie is the third article in the past 4 months to question the efficacy of family history as the first step in a screening strategy to identify children with hypercholesterolemia.1-3 Their finding that 50% of the children they identified with elevated low-density lipoprotein (LDL) cholesterol did not have a family history of premature cardiovascular disease or hyperlipidemia is essentially the same as that of Griffen and colleagues.2

Familial Hypercholesterolemia: Molecular, Biochemical, and Clinical Characterization of a French-Canadian Pediatric Population

PEDIATRICS ◽  
1995 ◽  
Vol 96 (2) ◽  
pp. 239-246
Author(s):  
Linda Assouline ◽  
Emile Levy ◽  
Juan Carlos Feoli-Fonseca ◽  
Caroline Godbout ◽  
Marie Lambert
Keyword(s):  
Ldl Cholesterol ◽  
Pediatric Population ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
French Canadian ◽  
Parental History ◽  
History Of ◽  
Group 3 ◽  
Group 1

Background. Familial hypercholesterolemia (FH) is a dominantly-inherited disorder attributable to a defect in the low-density lipoprotein (LDL) receptor gene. Five mutations at this locus have been identified in French-Canadians. In children, it may be difficult to clinically distinguish FH from other forms of polygenic or monogenic hyperlipidemia. Therefore, our objectives were to define the molecular basis of our subjects' hypercholesterolemia, to characterize their biochemical phenotype in relation to the underlying molecular defect, and to assess their response to chronic dietary therapy. Methods. We studied 88 unrelated French-Canadian children with a persistent increase in LDL cholesterol and a parental history of hyperlipidemia. Baseline and end-of-diet lipid and apolipoprotein levels were measured. Mutational analysis at the LDL receptor gene locus was performed. Results. Heterozygosity for the common French-Canadian LDL receptor gene >10-kb deletion was found in 57% of subjects (group 1), 14% carried one of the other four previously characterized LDL receptor gene mutations (group 2), and none of the five molecular defects tested was detected in 29% (group 3). Total cholesterol, LDL cholesterol, and apolipoprotein B baseline levels were similar among these three groups but significantly higher than in control subjects. However, there was wide interindividual variability even among those carrying the same mutation. Significantly lower baseline levels of high-density lipoprotein cholesterol and apolipoprotein A1 were found in group 1 compared with group 3 and the controls. The response to diet was similar among the three groups with an average reduction in the mean level of total cholesterol of 4.4%. Conclusions. The frequency of proven FH heterozygotes (71%) was remarkable in the pediatric population studied. Our data suggest that, in children, a persistent primary increase in LDL cholesterol associated with a parental history of hyperlipidemia is a good predictor of an underlying monogenic disorder as opposed to a polygenic disorder, at least in French-Canadians. Only molecular analysis allowed us to unequivocally define the cause of our patients' hypercholesterolemia. Most children with familial hyperlipidemia did not reach desirable plasma lipid levels solely under diet therapy.

scholarly journals Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment

2008 ◽  
Vol 54 (6) ◽  
pp. 1038-1045 ◽  
Author(s):  
Gilles Lambert ◽  
Nicolas Ancellin ◽  
Francesca Charlton ◽  
Daniel Comas ◽  
Julia Pilot ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Polyclonal Antibodies ◽  
Sandwich Elisa ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Diabetic Patients ◽  
Plasma Triglycerides ◽  
Fenofibrate Treatment ◽  
Before And After ◽  
Fenofibrate Intervention

Abstract Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment. Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment. Results: We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048). Conclusions: We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol–lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.

scholarly journals Predictors of Progressive Course of Multifocal Atherosclerosis in Patients With Myocardial Infarction

Kardiologiia ◽  
2019 ◽  
Vol 59 (5) ◽  
pp. 36-44 ◽  
Author(s):  
D. Yu. Sedykh ◽  
A. N. Kazantsev ◽  
R. S. Tarasov ◽  
V. V. Kashtalap ◽  
A. N. Volkov ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Family History ◽  
Syntax Score ◽  
Coronary Syndrome ◽  
History Of ◽  
One Year ◽  
Ica Stenosis ◽  
The Impact ◽  
Progression Of Atherosclerosis ◽  
Progressive Course

Purpose. Determination of clinical and instrumental predictors of progressive course of multifocal atherosclerosis (MFA) in patients one year after myocardial infarction (MI), initially having hemodynamically insignificant stenoses of carotid arteries.Materials and methods. From database of patients with acute coronary syndrome treated in the Kemerovo Regional Clinical Cardiac Dispensary in 2009–2010 we selected for this study 141 patients with verified diagnosis of MI and hemodynamically insignificant lesions in the internal carotid artery (ICA) (stenosis up ≤ 55 %). All patients had coronary atherosclerosis verified on coronary angiography at admission because of MI. A multivariate analysis of possible predictors of the progressive course of multifocal atherosclerosis was made based on assessment of the development of cardiovascular complications (CVC) (death, MI, stroke and transient cerebral circulatory attacks [TIA]), as well as revascularizations and negative dynamics of parameters of color duplex scanning (CDS) of ICA during one year after MI. Results. One year after MI the overall incidence of CVC was 16.3 % (n=23). Structure of registered events was as follows: death from MI 7.1 % (n=10), deaths from stroke 2.1 % (n=3) and other causes 2.1 % (n=3), non-fatal MI 5.0 % (n=7), non-fatal stroke / TIA 2.1 % (n=3), carotid revascularization 2.8 % (n=4), coronary revascularization 14.9 % (n=21). CDC of ICAs was repeated in 125 patients. There were 17 (13.6 %) cases of progression of carotid atherosclerosis in the form of de novo bilateral stenoses in 14 (11.2 %) patients, stenoses in the left and right ICA 1 patient and 2 patients, respectively. The following predictors of progression of atherosclerosis of cerebral arteries were identified: family history of cardiovascular diseases (CVD),ICA stenosis ≥45 %, baseline circular atherosclerotic plaque (ASP). Predictors of high risk of stroke were family history of CVD, history of stroke,ICA stenosis ≥45 %, heterogeneous hypoechoic ASP. As predictors of lethal outcome, we identified history of MI, high functional class of angina preceding the index MI, severe coronary vascular bed involvement (SYNTAX score >23), presence of any bilateral atherosclerotic lesion in ICAs, and heterogeneous hypoechoic ASP. Assessment of the contribution of adherence to therapy in the prognosis 1 year after hospital discharge was fulfilled in 125 alive patients. It allowed to conclude that patients with progression of atherosclerosis and nonfatal CVC were characterized by insufficient adherence to standard therapy.Conclusion. Predictors of the progressive course of multifocal atherosclerosis during one year after MI were identified in this study. It is necessary to strengthen therapeutic and preventive measures aimed at minimization of the impact of these factors in this category of patients.   

scholarly journals FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver

2018 ◽  
Vol 59 (6) ◽  
pp. 982-993 ◽  
Author(s):  
Romeo Papazyan ◽  
Xueqing Liu ◽  
Jingwen Liu ◽  
Bin Dong ◽  
Emily M. Plummer ◽  
...  
Keyword(s):  
Target Gene ◽  
Ldl Cholesterol ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Farnesoid X Receptor ◽  
Receptor Protein ◽  
Chimeric Mice ◽  
Obeticholic Acid ◽  
Protein Levels ◽  
Mechanistic Basis

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

Complex lipid-lowering treatment options in patients with a history of acute coronary syndrome

2011 ◽  
Vol 152 (8) ◽  
pp. 296-302 ◽  
Author(s):  
Győző Dani ◽  
László Márk ◽  
András Katona
Keyword(s):  
Acute Coronary Syndrome ◽  
Serum Lipid ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Coronary Syndrome ◽  
Target Values ◽  
History Of ◽  
Lipid Parameters

Authors aimed to assess how target values in serum lipid concentrations (LDL- and HDL-cholesterol, triglyceride) can be achieved in patients with a history of acute coronary syndrome during follow up in an outpatient cardiology clinic. Methods: 201 patients with a history of acute coronary syndrome were included and were followed up between January 1 and May 31, 2007.Authors analyzed serum lipid parameters of the patients and the lipid-lowering medications at the time of the first meeting and during follow up lasting two years. Results: During the enrollment visit only 26.4% of the patients had serum LDL cholesterol at target level, whereas high triglycerides and low HDL cholesterol levels were observed in 40.3% and 33.3% of the patients, respectively. Only 22 patients (10.9%) achieved the target levels in all three lipid parameters. Of the 201 patients, 179 patients participated in the follow up, and data obtained from these patients were analyzed. There was a positive trend toward better lipid parameters; 42.5% of the patients reached the desired LDL-cholesterol target value and 17.3% of the patients had HDL-cholesterol and triglycerides target values. Conclusions: These findings are consistent with those published in the literature. Beside the currently used therapeutic options for achieving optimal LDL-cholesterol, efforts should be made to reduce the so-called “residual cardiovascular risk” with the use of a widespread application of combination therapy. Orv. Hetil., 2011, 152, 296–302.

scholarly journals P747 Adherence to ECCO guidelines for cancer surveillance is associated to the detection of early cancer: A retrospective, single-centre, cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S598-S599
Author(s):  
T L PARIGI ◽  
G Roda PhD ◽  
M Allocca ◽  
F Furfaro ◽  
L Loy ◽  
...  
Keyword(s):  
Family History ◽  
Skin Cancer ◽  
Disease Duration ◽  
Early Cancer ◽  
Cancer Surveillance ◽  
Early Cancer Diagnosis ◽  
Increased Risk ◽  
Significant Difference ◽  
History Of ◽  
The Impact

Abstract Background Patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) are at increased risk of developing gastrointestinal (GI) malignancies. The aim of this study is to assess the risk of malignancies in IBD patients and the impact of cancer screening according to the ECCO guidelines in a tertiary referral centre. Methods We retrospectively analysed the electronic database of all IBD patients followed by the IBD Centre of Humanitas Research Hospital, Milan, from January 2010 to October 2019, and collected all new diagnoses of solid and haematological tumours since 2010. The annual standardised incidence rate (SIR), rate of mortality and early cancer diagnosis were calculated and a descriptive analysis of drug exposure, disease duration, family history of any cancer, smoking habits was made. Results We included 5239 patients, with a total 19820 patient-years follow-up. Eighty-four malignancies in 81 patients were retrieved, 71 were included in the final analysis (38 CD, 32 UC, 31 females). Average age at tumour diagnosis was 52.9 years (range 19–78). 64% of patients were former or active smokers, 31% had a family history of cancer or IBD. Sixty-two per cent of patients were previously exposed or had 5-ASA at the time of cancer, 40% azathioprine, 43% anti-TNF or vedolizumab. The annual SIR for all kinds of malignancy was 0.358%. GI malignancies were the most frequent (n = 17, 23.9%, 47% UC, 53% in CD). Six over 8 GI tract malignancies in UC patients were found in the colon or rectum (mean disease duration 22.5 years), whereas in CD patients 5/9 were in the small-bowel (mean disease duration 7.0 years). Melanoma and breast cancer (n = 8 each) were the most common non-GI cancers, followed by prostate (n = 7) and bladder (n = 6). No significant difference in incidence was found between CD or UC. Non-Hodgkin lymphomas and leukaemia (3 and 1, respectively) only occurred in CD patients. Other tumours included thyroid (n = 5), lungs (n = 4), testicle (n = 3), ovary (n = 2), kidney (n = 2), head-nose-throat (n = 2), pancreas (n = 1), brain (n = 1), and non-melanoma skin cancer (n = 1). Death occurred in 11% of patients, 8 of them for late stage cancer. Only 2 were related to the concomitant IBD (1 colo-rectal and 1 anal cancer). In patients regularly screened according to the ECCO Guidelines (GI cancer, haematological and skin cancer), there was a significantly higher number of detection of early cancer (28 vs. 1, p = 0.003), although no differences in mortality rates were reported in the two groups (2 vs. 2, p = 0.10). Conclusion The overall incidence of cancer in our cohort was not different from the current literature available. Adherence to the ECCO Guidelines for cancer surveillance improves the detection of early cancer in IBD patients.

Intraindividual Comparison of two Extracorporeal LDL Apheresis Methods: Lipidfiltration and HELP

2002 ◽  
Vol 25 (12) ◽  
pp. 1180-1188 ◽  
Author(s):  
U. Julius ◽  
W. Metzler ◽  
J. Pietzsch ◽  
T. Faßbender ◽  
R. Klingel
Keyword(s):  
Plasma Volume ◽  
Plasma Proteins ◽  
Ldl Cholesterol ◽  
Plasma Lipids ◽  
Plasma Heating ◽  
Hdl Cholesterol ◽  
The Novel ◽  
Ldl Apheresis ◽  
Effective Treatment Option ◽  
Plasma Therapy

Low density lipoprotein (LDL) apheresis is an effective treatment option for patients with severe hypercholesterolemia not adequately responding to diet and drug therapy. Membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP), here named Lipidfiltration, and heparin-induced extracorporeal LDL-precipitation (HELP) are two of the five methods available for extracorporeal LDL apheresis. In this prospective investigation 6 patients with severe LDL-hypercholesterolemia and CAD were treated in a cross-over design with Lipidfiltration at two stages of technical development and HELP to compare the efficacy of these two LDL apheresis methods with respect to lowering and modifying plasma lipids and rheologically relevant plasma proteins, especially fibrinogen. In total, 44 LDL apheresis sessions were investigated. In weekly intervals, patients were treated with consecutive LDL apheresis sessions with either Lipidfiltration and HELP, treating identical plasma volumes. In one part of the investigation Lipidfiltration was performed with the novel Lipidfilter EC-50, combined with a newly developed blood and plasma therapy machine allowing optimized plasma heating. The results showed that the reduction rates of LDL-cholesterol, lipoprotein(a) and triglycerides were essentially identical for both methods. Also pretreatment levels of total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were not significantly different in both treatment groups. Both methods lead to a significant reduction of serum lipoproteins, especially for LDL-cholesterol, which was decreased by 61.4% with Lipidfiltration (treated plasma volume: 2998 ml) and 61.3% with HELP (treated plasma volume: 3013 ml). With respect to Lipidfiltration LDL-cholesterol reduction was more efficient with the novel Lipidfilter EC-50. Mean pretreatment HDL cholesterol concentrations remained unchanged. Comparing Cascadeflo AC-1770 with the novel Lipidfilter EC-50 reduction rates of HDL-cholesterol (17.4% versus 6.4%) and total protein (17.9% versus 7.8%) were significantly reduced. Lipidfiltration and HELP both resulted in a reduction of plasma viscosity and hemorheologically relevant plasma proteins, like fibrinogen.

scholarly journals Serum adipocytokines and adiposity as predictive indices of preeclampsia

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Ahmed Tijani Bawah ◽  
Francis Agyemang Yeboah ◽  
Salifu Nanga ◽  
Huseini Alidu ◽  
Robert A. Ngala
Keyword(s):  
Family History ◽  
Pregnant Women ◽  
Heart Association ◽  
Hdl Cholesterol ◽  
First Trimester ◽  
Anthropometric Parameters ◽  
Family History Of Diabetes ◽  
Receiver Operating Characteristic Curves ◽  
Significant Difference ◽  
History Of

Abstract Background This study was aimed at determining the levels of serum adiponectin, leptin, resistin, visfatin and lipids during the first trimester in pregnant women and to evaluate the relationship between these biochemical markers and preeclampsia (PE). Available evidence point to changes in the levels of these adipokines in PE hence this study examined the potential of using these biomarkers in the prediction of the disease. Methods This was a case-control study which compared first trimester serum biochemical and anthropometric parameters in pregnant women who subsequently developed PE and those who did not. Blood pressure and urine protein were determined after 20 weeks of gestation and diagnosis of PE performed according to the guidelines of the American Heart Association. Results There was no significant difference (p > 0.05) in the lipid profile with the exception of HDL cholesterol which was significantly lower (p = 0.043) in the PE group compared to the normotensive group. There were, however, significant differences (p <  0.05) in the adipokines between the PE group and those without PE. Analyses of area under the receiver operating characteristic curves (AUCs) for the adipokines, showed their ability to correctly predict PE even after controlling for body mass index (BMI) and family history of hypertension. Conclusion Adiponectin, leptin, resistin and visfatin were found to be significant predictors of PE, with resistin being the best predictor after controlling for BMI. However, adiponectin was the best predictor after controlling for BMI, age, parity and family history of diabetes and preeclmapsia.

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