scholarly journals Familial hypercholesterolemia: case series of a rare condition

2021 ◽  
Vol 26 (3S) ◽  
pp. 4610
Author(s):  
O. P. Ishevskaia ◽  
A. M. Namitokov ◽  
S. V. Kruchinova ◽  
E. D. Kosmacheva
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Genetic Research ◽  
Case Series ◽  
Young Age ◽  
Diagnostic Methods ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy

Introduction. Cardiovascular events at a young age are often the first manifestation of a genetic disorder such as familial hypercholesterolemia. High cholesterol levels, xanthomas and xanthelasmas, as well as a positive family history of cardiovascular disease, make it possible to identify a group of patients subject to genetic research. The identification of a specific mutation helps to determine further strategy not only for a patient, but also to his or her immediate relatives, thereby effectively conducting both secondary and primary prevention of atherosclerosis complications.Brief description. Using the example of patients from the Krasnodar Lipid Center, the relevance of genetic testing and cascade screening is demonstrated. We show problems of delayed diagnosis and low medical adherence, as well as the ways to optimize care for patients with genetic lipid metabolism disorders.Discussion. The rise in the incidence of cardiovascular events at a young age in developed countries prompts the search for more improved screening and diagnostic methods for familial hypercholesterolemia. The optimal age of initiation of lipid-lowering therapy in children with established familial hypercholesterolemia is also discussed. While secondary prevention appears to be clearer, there is still insufficient achievement of low-density lipoprotein cholesterol targets in patients with a previous cardiovascular event.

Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy

2019 ◽  
Vol 12 (9) ◽  
pp. 1797-1804 ◽  
Author(s):  
Marcio H. Miname ◽  
Marcio Sommer Bittencourt ◽  
Sérgio R. Moraes ◽  
Rômulo I.M. Alves ◽  
Pamela R.S. Silva ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Coronary Artery Calcium ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

scholarly journals Statins for Children with Familial Hypercholesterolemia

2021 ◽  
Author(s):  
Dinara Sadykova ◽  
Liliia Galimova ◽  
Evgeniia Slastnikova ◽  
Zulfiia Khabibrakhmanova ◽  
Natalya Guseva
Keyword(s):  
Familial Hypercholesterolemia ◽  
World Literature ◽  
Genetic Disorder ◽  
Cumulative Effect ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Arterial Walls ◽  
Lowering Therapy ◽  
The World ◽  
Initiation Of Therapy

Familial hypercholesterolemia (FH) is the most common genetic disorder in the world. It is characterized by increased level of total cholesterol (TC), low-density lipoproteins (LDL-C) since childhood. The diagnosis and initiation of therapy are optimal in childhood before complications (aortic stenosis, atherosclerotic changes in the arterial walls) appear. The initiation of lipid-lowering therapy in FH since childhood is important to reduce the cumulative effect of LDL-C, to increase patient’s life expectancy. Statins are recommended as first-line drugs for treatment with monitoring of the recommended clinical, biochemical markers under the supervision of a physician. However, due to limited experience, there are differing opinions among clinicians regarding the age of initiation of lipid-lowering therapy. This review is an attempt to critically study the available data from the world literature concerning the use of statins in children with FH, their effectiveness, safety. It is important to determine the endpoints for determining the effectiveness of statins, such as lowering LDL-C, assessing the thickness of the intima-media complex. The frequency of occurrence of possible side effects in children is considered - diabetes mellitus, hepatotoxicity, muscle pain and others. There is a need to continue randomized trials to prove the lifelong benefit of low LDL-C in patients with FH.

Abstract 16263: Association Between Visit-to-Visit Lipid Variability and Cardiovascular Events in Patients With Familial Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yexuan Cao ◽  
Ruixia Xu ◽  
Huiwen Zhang ◽  
Jinglu Jin ◽  
Huihui Liu ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Prognostic Value ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Major Adverse Cardiovascular Events ◽  
Lipid Lowering Therapy ◽  
Cox Analysis

Introduction: Visit-to-visit variability in lipid has been suggested as an predictor of major adverse cardiovascular events (MACEs). However, no evidence exists on the prognostic value of lipid variability in patients with familial hypercholesterolemia (FH). Hypothesis: This prospective cohort study aimed to investigate whether lipid variability affects future MACEs in patients with FH receiving standard lipid-lowering therapy. Methods: A total of 254 patients with FH were consecutively enrolled and followed for MACEs. Variability in triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] were evaluated from 3 months after discharge using the standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM). Results: During a mean follow-up of 49 months, 22 (8.7%) events occurred. Visit-to-visit variability in Lp(a) was significantly higher in the MACE group compared to the non-MACE group. In multivariate Cox analysis, only Lp(a) variability parameters were independent predictors for MACEs. The hazard ratios and 95% confidence intervals of each 1-SD increase of SD, CV and VIM of Lp(a) were 1.42 (1.12-1.80), 1.50 (1.11-2.02) and 1.60 (1.16-2.22), respectively. Kaplan-Meier analysis revealed that patients with higher Lp(a) variability presented lower event-free survival (Log-rank p <0.05). The results were consistent in various subgroups. Conclusions: This is the first report to evaluate the prognostic value of lipid variability in real-world patients with FH and showed that Lp(a), but not LDL-C variability, was associated with MACEs, which emphasized the importance of regular lipid monitoring in patients with high risk.

Abstract 3699: Efficacy and Safety of Colesevelam HCl in Pediatric Patients with Heterozygous Familial Hypercholesterolemia

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Evan A Stein ◽  
David Marais ◽  
Tamas Szamosi ◽  
Frederick Raal ◽  
Daniel Schurr ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Lipid Lowering ◽  
Controlled Study ◽  
Lipid Lowering Therapy ◽  
Efficacy And Safety ◽  
Degree Relative ◽  
Double Blind ◽  
Heterozygous Familial Hypercholesterolemia

Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder resulting in elevated LDL-C, which confers a high risk for a coronary event. Colesevelam HCl (COL), a non-absorbable bile acid sequestrant, is approved to lower LDL-C in adults with primary hypercholesterolemia. This is the first data demonstrating the efficacy and safety of COL in pediatric pts with heFH. This 32wk multicenter, randomized, double-blind (DB), placebo (PLA)-controlled study included: a 4wk PLA run-in (to measure compliance); an 8wk DB period (pts randomized 1:1:1 to PLA, 1.875 g/d COL, or 3.75 g/d COL); an 18wk open-label (OL) treatment to goal (LDL-C <110 mg/dL) wherein all pts received COL 3.75 g/d (and were eligible to receive a statin); and a 2wk follow-up. Males and females, aged 10 –17yrs, with either genetic diagnosis of heFH or history of untreated LDL-C >160 mg/dL combined with familial dyslipidemia in a first degree relative, who had a baseline LDL-C >160 mg/dL (if naíve to lipid-lowering therapy) or >130 mg/dL (if on a statin [≥6wks]) and following a NCEP step 1 diet were included. Additional inclusion criteria were TG <250 mg/dL, ≥Tanner stage 2, and compliance ≥75% during the PLA run-in. Primary efficacy parameter was % change in LDL-C from baseline/Day 1 to Wk 8. The ITT population (randomized pts with a baseline and ≥1 post-baseline measurement) was used to evaluate efficacy parameters. Of the 194 pts randomized, 95.9% and 89.2% completed the DB and OL periods, respectively. Approximately 25% were on a statin at entry into the DB period; a further 10% added a statin during the OL period. At wk 8, LDL-C, TC, and apoB significantly decreased while HDL-C and apoA-I significantly increased with COL 3.75 g/d ( P <0.01 vs PLA for all; Table ). Adverse events were as expected; no choking was recorded. No effects were noted on growth, sexual maturation, hormone levels, absorption of fat-soluble vitamins, or clotting parameters. In summary, COL lowered LDL-C and was well tolerated in pediatric pts.

Plasma proprotein convertase subtilisin/kexin type 9 concentration and recurrent cardiovascular events in patients with familial hypercholesterolemia

2019 ◽  
pp. 204748731988098 ◽  
Author(s):  
Ye-Xuan Cao ◽  
Hui-Hui Liu ◽  
Jing-Lu Jin ◽  
Di Sun ◽  
Yuan-Lin Guo ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Confidence Interval ◽  
Familial Hypercholesterolemia ◽  
Coronary Artery Calcification ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lipid Lowering Therapy ◽  
Gensini Score ◽  
Proprotein Convertase

Aims Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined. Methods A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval. Results Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan–Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11–1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events. Conclusions Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.

scholarly journals Lipoprotein(a) and Cardiovascular Outcomes after Revascularization of Carotid and Lower Limbs Arteries

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 257
Author(s):  
Marat V. Ezhov ◽  
Narek A. Tmoyan ◽  
Olga I. Afanasieva ◽  
Marina I. Afanasieva ◽  
Sergei N. Pokrovsky
Keyword(s):  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Cardiovascular Outcomes ◽  
Lower Limbs ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cox Regression Analysis ◽  
Lipoprotein A ◽  
Secondary Endpoints

Background: Despite high-intensity lipid-lowering therapy, there is a residual risk of cardiovascular events that could be associated with lipoprotein(a) (Lp(a)). It has been shown that there is an association between elevated Lp(a) level and cardiovascular outcomes in patients with coronary heart disease. Data about the role of Lp(a) in the development of cardiovascular events after peripheral revascularization are scarce. Purpose: To evaluate the relationship of Lp(a) level with cardiovascular outcomes after revascularization of carotid and lower limbs arteries. Methods: The study included 258 patients (209 men, mean age 67 years) with severe carotid and/or lower extremity artery disease, who underwent successful elective peripheral revascularization. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary endpoint was the composite of primary endpoint and repeated revascularization. Results: For 36-month follow-up, 29 (11%) primary and 128 (50%) secondary endpoints were registered. There was a greater risk of primary (21 (8%) vs. 8 (3%); hazard ratio (HR), 3.0; 95% confidence interval (CI) 1.5–6.3; p < 0.01) and secondary endpoints (83 (32%) vs. 45 (17%), HR, 2.8; 95% CI 2.0–4.0; p < 0.01) in patients with elevated Lp(a) level (≥30 mg/dL) compared to patients with Lp(a) < 30 mg/dL. Multivariable-adjusted Cox regression analysis revealed that Lp(a) was independently associated with the incidence of cardiovascular outcomes. Conclusions: Patients with peripheral artery diseases have a high risk of cardiovascular events. Lp(a) level above 30 mg/dL is significantly and independently associated with cardiovascular events during 3-year follow-up after revascularization of carotid and lower limbs arteries.

scholarly journals FAMILIAL HYPERCHOLESTEROLEMIA: DIAGNOSTIC ISSUES AND THERAPEUTIC POSSIBILITIES

2019 ◽  
Vol 26 (1) ◽  
pp. 175-186
Author(s):  
Vitalii K. Zafiraki ◽  
Alim M. Namitokov ◽  
Elena D. Kosmacheva
Keyword(s):  
Familial Hypercholesterolemia ◽  
Conflict Of Interest ◽  
Screening Program ◽  
Genetic Defect ◽  
Clinical Manifestations ◽  
Density Lipoprotein ◽  
Premature Death ◽  
Lipid Lowering ◽  
Monogenic Disease ◽  
Lipid Lowering Therapy

Familial hypercholesterolemia (FHC) is a common monogenic disease that occurs with a frequency of ~1:250 and is characterised by a high content of low-density lipoprotein (LDL) in the blood. This disease leads to the early development of atherosclerotic cardiovascular diseases (ACVD). Although the screening and diagnostics issues concerned with FHC are well developed and the modern lipid-lowering therapy can significantly improve the prognosis, the detectability of this disease remains extremely low. In recent years, the concept of FHC has undergone significant changes under the influence of large epidemiological studies, including verification of the FHC diagnosis using genetic tests. The article is aimed at discussing the clinical manifestations of FHC, as well as modern medical and extracorporal approaches to its treatment.Conclusion.Until the advent of modern lipid-lowering drugs, FHC had remained to be a disease with a poor prognosis due to early ACVD and the associated premature death. Today, the diseases is amenable to successful treatment, which, though not eliminating the genetic defect, allows almost the same life duration as in the general population to be achieved. However, all the possibilities of modern approaches to the treatment of this serious disease can be realized provided that a state-level screening program for such patients has been implemented.Conflict of interest: the authors declare no conflict of interest.

Abstract 18995: Statins in Familial Hypercholesterolemia - Effects on Coronary Artery Disease and All-cause Mortality

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Joost Besseling ◽  
Gerard K Hovingh ◽  
John J Kastelein ◽  
Barbara A Hutten
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Familial Hypercholesterolemia ◽  
Lipid Lowering ◽  
Premature Coronary Artery Disease ◽  
Lipid Lowering Therapy ◽  
Time Varying ◽  
All Cause Mortality ◽  
Artery Disease

Introduction: Heterozygous familial hypercholesterolemia (heFH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary artery disease (CAD) and death. Reduction of CAD and mortality by statins has not been properly quantified in heFH. The aim of the current study is to determine the effect of statins on CAD and mortality in heFH. Methods: All adult heFH patients identified by the Dutch FH screening program between 1994 and 2014 and registered in the PHARMO Database Network were eligible. Of these patients we obtained hospital, pharmacy (in- and outpatient), and mortality records in the period between 1995 and 2015. The effect of statins (time-varying) on CAD and all-cause mortality was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, antihypertensive and antidiabetic medication (all time-varying). Furthermore, we used inverse probability for treatment weighting (IPTW) to account for differences between statin-treated and untreated patients regarding history of CAD before follow-up, age at start of follow-up and age of screening, as well as body mass index, LDL-C and triglycerides. Results: Of the 25,479 identified heFH patients, 11,021 gave informed consent to obtain their medical records, of whom 2,447 could be retrieved. We excluded 766 patients younger than 18. The remaining 1,681 heFH patients comprised our study population and these had very similar characteristics as compared to the 23,798 excluded FH patients, e.g. mean (SD) LDL-C levels were 214 (74) vs. 203 (77) mg/dL. Among 1,151 statin users, there were 133 CAD events and 15 deaths during 10,115 statin treated person-years, compared to 17 CAD events and 9 deaths during 4,965 person-years in 530 never statin users (combined rate: 14.6 vs. 5.2, respectively, p<0.001). After applying IPTW to account for indication bias and correcting for use of other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.61 (0.40 - 0.93). Conclusions: In heFH patients, statins lower the risk for CAD and mortality by 39%.

P938Extensive formation of atherosclerotic cardiovascular disease in subjects with severe familial hypercholesterolemia defined by the international atherosclerosis society criteria

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Funabashi ◽  
Y Kataoka ◽  
M Harada-Shiba ◽  
M Hori ◽  
T Doi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Peripheral Artery Disease ◽  
Cardiac Death ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Peripheral Artery ◽  
Lowering Therapy ◽  
Artery Disease

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C>10.3 mmol/l, LDL-C>8.0 mmol/l+ 1 high-risk feature, LDL-C>4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction>50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 <0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] <0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction>50% 21.3% 49.8% <0.0001 High-intensity statin (%) 13.3% 42.3% <0.0001 PCSK9 inhibitor (%) 6.3% 21.2% <0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.

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