scholarly journals The UK Paediatric Familial Hypercholesterolaemia Register: preliminary data

2016 ◽  
Vol 102 (3) ◽  
pp. 255-260 ◽  
Author(s):  
Uma Ramaswami ◽  
Jackie Cooper ◽  
Steve E Humphries
Keyword(s):  
Family History ◽  
Familial Hypercholesterolaemia ◽  
Age Groups ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Baseline Data ◽  
Degree Relative ◽  
History Of ◽  
The Uk

BackgroundThe National Institute for Health and Care Excellence 2008 guidelines on the treatment and management of familial hypercholesterolaemia (FH) recommend that children with FH should be considered for statin treatment by the age of 10 years. The Paediatric FH Register was established in 2012 to collect baseline and long-term follow-up data on all children with FH in the UK.MethodsPaediatricians and adult lipidologists have been invited to enter baseline data on any child with a clinical diagnosis of FH using an electronic capture record.ResultsBaseline data is on 232 children (50% boys, 80% Caucasian), with an untreated mean (SD) total cholesterol of 7.61 (1.48) mmol/L and low-density lipoprotein cholesterol (LDL-C) of 5.67 (1.46) mmol/L. Overall 111/232 (47.8%) of the children were on statins. Children over the age of 10 years at the most recent follow-up were twice as likely to be on statin treatment than those under 10 years (57.6% (102/177) vs 23.1% (9/39), p=0.00009). In both age groups, those subsequently on statin treatment had significantly higher diagnostic total and LDL-C (overall 6.01 (1.46) mmol/L vs 5.31 (1.37) mmol/L, p=0.00007), and had stronger evidence of a family history of early coronary heart disease (CHD) in parent or first-degree relative (overall 28.4% vs 19.0%, p=0.09). In statin-treated children LDL-C level was reduced by 35% (2.07 (1.38) mmol/L) compared with a reduction of 5.5% (0.29 (0.87) mmol/L), p=0.0001 in those not treated. None of those on statin had measured plasma levels of creatine kinase, alanine aminotransferase and AST indicative of statin toxicity (ie, >2.5 times the upper limit of the normal range).ConclusionsThe data indicates that treatment decisions in children with FH are appropriately based on a stronger family history of CHD and higher LDL-C.

scholarly journals 22-year longitudinal study of repetitive colonoscopy in patients with a family history of colorectal cancer

2013 ◽  
Vol 95 (8) ◽  
pp. 586-590 ◽  
Author(s):  
JK Randall ◽  
CS Good ◽  
JM Gilbert
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
British Society ◽  
Degree Relative ◽  
Surveillance Programme ◽  
Patients With Cancer ◽  
Significant Pathology ◽  
History Of

Introduction We report the outcomes of a long-term surveillance programme for individuals with a family history of colorectal cancer. Methods The details of patients undergoing a colonoscopy having been referred on the basis of family history of colorectal cancer were entered prospectively into a database. Further colonoscopy was arranged on the basis of the findings. The outcomes assessed included incidence of cancer and adenoma identification at initial and subsequent colonoscopy. Results The records of 2,293 patients (917 men; median patient age: 51 years) were entered over 22 years, giving data on 3,982 colonoscopies. Eight adverse events (0.2%) were recorded. Twenty-seven cancers were found at first colonoscopy and thirteen developed during the follow-up period. There were significantly more cancers identified in those with more than one first-degree relative with cancer than in other groups (p=0.01). The number of adenomas identified at subsequent surveillance colonoscopies remained constant with between 9.3% and 12.0% of patients having adenomas that were removed. Two-thirds (68%) of patients with cancer and three-quarters (77%) with adenomas fell outside the British Society of Gastroenterology (BSG) 2006 guidelines. Conclusions Repeated colonoscopy continues to yield significant pathology including new cancers. These continue to occur despite removal of adenomas at prior colonoscopies. The majority of patients with cancers and adenomas fell outside the BSG 2006 guidelines; more would have fallen outside the 2010 guidelines.

Value of Childhood Blood Pressure Measurements and Family History in Predicting Future Blood Pressure Status: Results From 8 Years of Follow-up in the Bogalusa Heart Study

PEDIATRICS ◽  
1986 ◽  
Vol 77 (6) ◽  
pp. 862-869 ◽  
Author(s):  
Charles L. Shear ◽  
Gregory L. Burke ◽  
David S. Freedman ◽  
Gerald S. Berenson
Keyword(s):  
Blood Pressure ◽  
Family History ◽  
Age Groups ◽  
Correlation Coefficients ◽  
Pressure Measurements ◽  
Bogalusa Heart Study ◽  
Heart Study ◽  
History Of ◽  
Family History Of Hypertension

The value of BP measurements and family history of cardiovascular disease in predicting future BP status was studied in 1,501 children, initially 2 to 14 years of age, who were examined four times during an 8-year period in the Bogalusa Heart Study. Correlation coefficients between year 1 and year 9 BPs were as follows for systolic and diastolic BPs, respectively: 0.41 and 0.35 (P < .0001). These correlations were significant in all age groups. For children in the upper quartile of BP at any one prior examination, the percentage remaining in the year 9 upper quartile ranged from 41% to 52% for systolic BP and 35% to 44% for diastolic BP. Three serial BP measurements in the upper quartile increased the percentages remaining in the upper quartile to 68% for systolic BP and 62% for diastolic BP. Conversely, of those children not in the upper quartile of systolic BP at year 9, 96.8% did not have all three prior measurements in the upper quartile. Family history of hypertension was shown to independently predict year 9 systolic BP status. These results confirm the importance of serial BP measurements and family history of hypertension for the practicing physician.

P890Gene carriers of hypertrophic cardiomyopathy, what to expect over time

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Poveda Velazquez ◽  
J Basu ◽  
T Homfray ◽  
M Papadakis ◽  
E Behr ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Family History ◽  
Age Groups ◽  
Gene Mutations ◽  
Left Ventricular ◽  
Cascade Screening ◽  
Cardiac Symptoms ◽  
History Of ◽  
Mybpc3 Gene

Abstract Background Data on the natural history of genotype positive/phenotype negative (G+/P-) hypertrophic cardiomyopathy (HCM) patients identified as a part of genetic cascade screening in different age groups is limited. Purpose To describe the rate of conversion to overt HCM phenotype in G+/P- subjects in relation with the age who were identified in a specialized clinic in a single center. Methods We retrospectively identified 56 consecutive HCM G+/P− subjects followed in our center specialized clinic between Jan 2012-Jan 2019. Demographics, family history of sudden cardiac death (SCD) and presence of symptoms were collected. All of them underwent baseline investigations including ECG, echocardiogram and/or cardiac magnetic resonance (CMR) and 24 hour monitor at baseline and during follow up. Overt HCM phenotype was defined as left ventricular hypertrophy (LVH) ≥13mm in the echocardiogram or CMR. Results We identified 56 HCM G+/P− subjects from 34 different families. 22 subjects were ≤18 years old with a mean age of 11.6±0.9 years (IQR [P25-P75] 9–16 years) and 32 subjects were >18 years old with a mean age of 38.1±2.2 years (IQR [P25-P75] 27–48 years). Mean time of follow up was 35.2±34.4 months (IQR [P25-P75] 4.25–50.25 years). 60.7% (34) of them were female and 82.1% (46) were of Caucasian ethnicity. Most of the subjects with no evidence LVH were asymptomatic but small number had symptoms, 8.9% (5), and 3.6% (2) were treated with betablockers for palpitations. Family history of SCD was present in 57.1% (32) of the subjects and 35.7% (20) had a relative with an implantable cardiac defibrillator (ICD). MYBPC3 gene mutations were identified in 62.5% (35) of subjects, followed by MYH7 gene mutation in 23.2% (13) of the cases. None of the subjects under 18 year old developed HCM during the period of observation, however 7 subjects (21.9%), mean age 48.6±10.5 years, 71.4% (5) females, showed progression to HCM in the >18 years old group. All of them had pathogenic MYBPC3 gene variants. No differences were found in gender, ethnicity, symptoms or family history of SCD in the G+/P− vs HCM group. There were no differences on the presence of ECG abnormalities and no episodes of NSVT were recorded in any of the groups. Baseline E/e' values of those with new HCM vs G+/P− were higher (8.2±3.3 vs 5.6±1.7, p=0.014). Conclusions In our cohort, rate of progression to HCM phenotype was 21.9% of >18 years old HCM G+/P- subjects. The mean age at the time of developing the phenotype was 48.6±10.5 years old and all the patients were asymptomatic for cardiac symptoms. Echocardiographic E/e' values were increased. This data supports the need of life long follow up of this group of patients with ongoing clinical evaluation. Acknowledgement/Funding ESC clinical grant

scholarly journals Long term CMR follow up of patients with right ventricular abnormality and clinically suspected arrhythmogenic right ventricular cardiomyopathy (ARVC)

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Giuseppe Femia ◽  
Christopher Semsarian ◽  
Mark McGuire ◽  
Raymond W. Sy ◽  
Rajesh Puranik
Keyword(s):  
Family History ◽  
Ejection Fraction ◽  
Right Ventricular ◽  
Task Force ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Premature Death ◽  
Ventricular Cardiomyopathy ◽  
Degree Relative ◽  
History Of

Abstract Background The Task Force Criteria (TFC) for arrhythmogenic right ventricular cardiomyopathy (ARVC) was updated in 2010 to improve specificity. There was concern however that the revised cardiovascular magnetic resonance (CMR) criteria was too restrictive and not sensitive enough to detect early forms of the condition. We previously described patients with clinically suspected ARVC who satisfied criteria from non-imaging TFC categories and fulfilled parameters from the original but not the revised CMR criteria; as a result, these patients were not confirmed as definite ARVC but may represent an early phenotype. Methods Patients scanned between 2008 and 2015 who had either right ventricular (RV) dilatation or regional dyskinesia satisfying at least minor imaging parameters from the original criteria and without contra-indication underwent serial CMR scanning using a 1.5 T scanner. The aims were to assess the risk of progressive RV abnormalities, evaluate the accuracy of the revised CMR criteria and the need for guideline directed CMR surveillance in at-risk individuals. Results Overall, 48 patients were re-scanned; 24 had a first-degree relative diagnosed with ARVC using the revised TFC or a first-degree relative with premature sudden death from suspected ARVC and 24 patients had either left bundle branch morphology ventricular tachycardia or > 500 ventricular extra-systoles in 24-h. Mean follow up was 69+/− 25 months. The indexed RV end-diastolic, end-systolic volumes and ejection fraction were calculated for both scans. There was significant reduction in RV volumes and improvement in RV ejection fraction (EF) irrespective of changes to body surface area; − 11.7+/− 15.2 mls/m2, − 6.4+/− 10.5 mls/m2 and + 3.3 +/− 7.9% (p = 0.01, 0.01 and 0.04). Applying the RV parameters to the revised CMR criteria, two patients from the family history group (one with confirmed ARVC and one with a premature death) had progressive RV abnormalities satisfying major criteria. The remaining patients (n = 46) did not satisfy the criteria and either had normal RV parameters with regression of structural abnormalities (27,56.3%) or stable abnormalities (19,43.7%). Conclusion The revised CMR criteria represents a robust tool in the evaluation of patients with clinical suspicion of ARVC, especially for those with ventricular arrhythmias without a family history for ARVC. For patients with RV abnormalities that do not fulfill the revised criteria but have a family history of ARVC or an ARVC associated gene mutation, a surveillance CMR scan should be considered as part of the clinical follow up protocol.

scholarly journals Apolipoprotein E polymorphism and changes in serum lipids during a family-based counselling intervention

2006 ◽  
Vol 9 (7) ◽  
pp. 859-865 ◽  
Author(s):  
Marika Salminen ◽  
Terh Lehtimäki ◽  
Yue-Mei Fan ◽  
Tero Vahlberg ◽  
Sirkka-Liisa Kivelä
Keyword(s):  
Family History ◽  
Health Education ◽  
Apolipoprotein E ◽  
Serum Lipids ◽  
Risk Group ◽  
Density Lipoprotein ◽  
History Of ◽  
E4 Allele ◽  
Family Based

AbstractObjectiveTo compare serum lipids and their changes during a family-based health education in children aged 6–17 years with or without the ɛ4 allele of the gene encoding apolipoprotein E (apoE).DesignAn intervention study.SettingA family-based prevention of risk factors of coronary heart disease in Eastern Finland. The programme consisted of two counselling meetings at children's schools and three at children's homes.SubjectsFour hundred and thirty-nine children with a family history of cardiovascular diseases (CVD) participated in a family-based health education. The children were divided into two groups according toapoEgenotype. The risk group consisted of 143 children havingapoEɛ4 allele (genotype ɛ3/4 or ɛ4/4) and the non-risk group of 296 children withoutapoEɛ4 allele (ɛ2/3 or ɛ3/3). The final sample of the follow-up study included 354 (81%) children (114 and 240, respectively).ResultsBaseline differences were found in low-density lipoprotein cholesterol (LDL-C) (P= 0.007) and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio (P= 0.030) among boys and in total cholesterol (TC)/HDL-C (P= 0.008) and LDL-C/HDL-C ratios (P= 0.006) among girls. Differences between groups in changes during the follow-up were observed only for TC/HDL-C ratio (P-value adjusted for age = 0.049) among boys.ConclusionsAt baseline, children withapoEɛ4 allele had on average a more unfavourable lipid profile than those withoutapoEɛ4 allele. However, the effect of about 33 months' family-based health education on plasma lipids did not depend onapoEgenotype in children with a family history of CVD.

The consumption of cigarettes, coffee and sweets in detoxified alcoholics and its association with relapse and a family history of alcoholism

2005 ◽  
Vol 20 (5-6) ◽  
pp. 451-455 ◽  
Author(s):  
Klaus Junghanns ◽  
Jutta Backhaus ◽  
Ulrike Tietz ◽  
Wolfgang Lange ◽  
Lothar Rink ◽  
...  
Keyword(s):  
Family History ◽  
Depressive Disorder ◽  
Inpatient Treatment ◽  
Positive Family History ◽  
Coffee Consumption ◽  
Degree Relative ◽  
History Of ◽  
Discharge From Hospital ◽  
Alcohol Dependent

AbstractThirty male alcohol dependent inpatients without concurrent depressive disorder, 13 of them with a positive family history of alcohol dependence in a first degree relative (PFH), were questioned about their desire and consumption habits with respect to cigarettes, coffee, and sweets while on a three-week inpatient treatment after detoxification from alcohol. Six weeks after discharge from hospital, the patients were reassessed for relapse. Eleven patients (36.6%) had relapsed at follow-up. Relapsers were younger than abstainers. The days until relapse correlated negatively with intensity of desire to drink alcohol, desire to smoke cigarettes, and with a higher consumption of cigarettes. PFH patients did not relapse earlier but they had a stronger desire to drink coffee and eat sweets and had a higher coffee consumption.

scholarly journals Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis

Kardiologiia ◽  
2021 ◽  
Vol 61 (1) ◽  
pp. 12-21
Author(s):  
O. A. Fomicheva ◽  
T. V. Popkova ◽  
L. B. Krougly ◽  
E. V. Gerasimova ◽  
D. S. Novikova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Family History ◽  
Prospective Study ◽  
Proinflammatory Cytokines ◽  
Comparison Group ◽  
Density Lipoprotein ◽  
Tnf Α ◽  
History Of ◽  
Progression Of Atherosclerosis

Aim      To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods  This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (<1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p<0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p<0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was >50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion      Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

scholarly journals Prediction of subclinical coronary atherosclerosis in patients with high and very high cardiovascular risk

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
N Pogosova ◽  
NP Kachanova ◽  
YM Yufereva ◽  
OY Sokolova ◽  
IE Koltunov ◽  
...  
Keyword(s):  
Family History ◽  
Ct Angiography ◽  
Coronary Atherosclerosis ◽  
Subclinical Atherosclerosis ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Diagnostic Model ◽  
History Of ◽  
Hs Crp ◽  
Very High

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary atherosclerosis has a long subclinical period. It’s early detection may offer a possibility of timely initiation of preventive interventions Purpose To develop a diagnostic rule for detection of patients (pts) with high probability of subclinical atherosclerosis among those with high or very high cardiovascular (CV) risk. Methods This cross-sectional study enrolled 52 pts (32 men [62%]), aged 40 to 65 years [mean age 54.6 ± 8.0]) with high or very high CV risk (5-9 and ≥10% by The Systematic Coronary Risk Estimation Scale [SCORE], respectively). All participants underwent cardiac computed tomography (CT) angiography and calcium scoring. Traditional risk factors (RFs) (family history of premature CVD, smoking, overweight/obesity and abdominal obesity, hypertension, type 2 diabetes mellitus, lipids parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides) and lipids-related markers (apolipoprotein A1, apolipoprotein B, ApoB/ApoA1 ratio), biomarkers of inflammation (high-sensitivity C-reactive protein [hs CRP], fibrinogen), indicator carbohydrate metabolism (glucose),  ankle-brachial index,  stress-test, carotid plaques according to ultrasound were evaluated in all pts. Psychological RFs were evaluated using Hospital Anxiety and Depression Scale and DS-14 for type D personality. Results All pts were divided into 2 groups according to the CT angiography results: pts in the main group (n = 21) had any non-obstructive lesions or calcium score &gt;0, pts in the control group (n = 31) had intact coronary arteries. The groups did not differ in age or gender. 26 multiple linear logistic models for any subclinical atherosclerosis were developed based on obtained diagnostic features. Taking into account R-square = 0.344 (p = 0.0008), the best fitting model was follows:  subclinical coronary atherosclerosis= -1.576 + 0.234 x SCORE ≥5%  + 0.541 x hs CRP &gt;2 g/l + 0.015 x heart rate  (bpm) + 0.311 family history of premature CVD.  The developed algorithm had sensitivity of 63% and  specificity of 80%. Conclusions The created diagnostic model diagnostic model suggests the presence of subclinical coronary atherosclerosis in patients with high / very high CV risk with a high degree of probability. This easy-to-use method can be used in routine clinical practice to improve risk stratification and management choices in high-risk pts.

scholarly journals Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

2021 ◽  
Vol 9 (1) ◽  
pp. e001948
Author(s):  
Marion Denos ◽  
Xiao-Mei Mai ◽  
Bjørn Olav Åsvold ◽  
Elin Pettersen Sørgjerd ◽  
Yue Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Family History ◽  
Genetic Predisposition ◽  
Effect Modification ◽  
P Value ◽  
Family History Of Diabetes ◽  
Increased Risk ◽  
History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

scholarly journals Eculizumab discontinuation in atypical hemolytic uremic syndrome: TMA recurrence risk and renal outcomes

2021 ◽  
Author(s):  
Gema Ariceta ◽  
Fadi Fakhouri ◽  
Lisa Sartz ◽  
Benjamin Miller ◽  
Vasilis Nikolaou ◽  
...  
Keyword(s):  
Family History ◽  
Hemolytic Uremic Syndrome ◽  
Univariate Analysis ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Renal Response ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
History Of ◽  
Uremic Syndrome

ABSTRACT Background Eculizumab modifies the course of disease in patients with atypical hemolytic uremic syndrome (aHUS), but data evaluating whether eculizumab discontinuation is safe are limited. Methods Patients enrolled in the Global aHUS Registry who received ≥1 month of eculizumab before discontinuing, demonstrated hematologic or renal response prior to discontinuation and had ≥6 months of follow-up were analyzed. The primary endpoint was the proportion of patients suffering thrombotic microangiopathy (TMA) recurrence after eculizumab discontinuation. Additional endpoints included: eGFR changes following eculizumab discontinuation to last available follow-up; number of TMA recurrences; time to TMA recurrence; proportion of patients restarting eculizumab; and changes in renal function. Results We analyzed 151 patients with clinically diagnosed aHUS who had evidence of hematologic or renal response to eculizumab, before discontinuing. Thirty-three (22%) experienced a TMA recurrence. Univariate analysis revealed that patients with an increased risk of TMA recurrence after discontinuing eculizumab were those with a history of extrarenal manifestations prior to initiating eculizumab, pathogenic variants, or a family history of aHUS. Multivariate analysis showed an increased risk of TMA recurrence in patients with pathogenic variants and a family history of aHUS. Twelve (8%) patients progressed to end-stage renal disease after eculizumab discontinuation; 7 (5%) patients eventually received a kidney transplant. Forty (27%) patients experienced an extrarenal manifestation of aHUS after eculizumab discontinuation. Conclusions Eculizumab discontinuation in patients with aHUS is not without risk, potentially leading to TMA recurrence and renal failure. A thorough assessment of risk factors prior to the decision to discontinue eculizumab is essential.

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