Abstract 406: Achievement of Treatment Target in Korean Patients With Familial Hypercholesterolemia

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chan Joo Lee ◽  
Jaewon Oh ◽  
Jung Sun Kim ◽  
Sang-Hak Lee
Keyword(s):  
Total Cholesterol ◽  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Treatment Target ◽  
Evaluation Point ◽  
The Mean ◽  
Artery Disease ◽  
Primary Evaluation

Background: In many cases of familial hypercholesterolemia (FH), there remains difficulty in achievement of treatment target. However, despite growing attention to FH, data on the treatment and its results in these patients are very limited. Methods: From nine sites in Korea, 122 consecutive unrelated men and women who were diagnosed with heterozygous FH by Simon Broome criteria were initially enrolled. Atorvastatin 20 mg or similar-potency drugs were prescribed and the dose was escalated every 2 months (for the first 6 months) or 6 months (thereafter) if needed. Forty one subjects were dropped and 81 subjects who underwent regular laboratory check-up were finally analyzed. The primary evaluation points were achievement rates of low-density lipoprotein cholesterol (LDL-C) <70 mg/dL, LDL-C<100 mg/dL, and LDL-C down to 50% of baseline levels at 12 month. The secondary evaluation point was % change of LDL-C at 12 month. Results: Patients’ mean age was 53 years and 59.3% were males. 21.0% were definite type FH and 28.4% had coronary artery disease (CAD). The mean total cholesterol and LDL-C were 319 mg/dL and 232 mg/dL, respectively. At 12 month, 7.4% received atorvastatin 10mg or similar, 21.0% received atorvastatin 20mg or similar, 16.0% received atorvastatin 40mg or similar, 4.9% received atorvastatin 80mg or similar, and 49.4% received atorvastatin (mean 57 mg) or similar plus ezetimibe 10mg. The mean follow-up total cholesterol and LDL-C were 201 mg/dL and 124 mg/dL, respectively. The mean % change of LDL-C was -45.6%. The achievement rates of LDL-C<70 mg/dL, <100 mg/dL, and LDL-C down to 50% of baseline were 1%, 21%, and 44%, respectively. The achievement rates were not significantly different between the patients without or with CAD (1.8%, 26.3%, 47.4% vs. 0%, 8.7%, 34.8%, respectively, all p values > 0.05). Conclusions: The achievement rate of treatment target in FH was low in Korea even after maximum tolerable dose of lipid lowering drugs. Improvement of awareness on this issue and more aggressive treatment are needed for this population.

Abstract 14270: The Effect of Evinacumab on Apheresis Eligibility in Patients With Homozygous Familial Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Frederick J Raal ◽  
Robert S Rosenson ◽  
Laurens F Reeskamp ◽  
G. Kees Hovingh ◽  
John J Kastelein ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Human Monoclonal Antibody ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Homozygous Familial Hypercholesterolemia ◽  
Double Blind ◽  
Lipid Disorder ◽  
Artery Disease

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Evinacumab, a fully human monoclonal antibody against angiopoietin-like protein 3, has demonstrated approximately 50% reductions in LDL-C in HoFH patients when added to maximally tolerated lipid-lowering therapies. Objective: In this post-hoc analysis, we assessed the effect of evinacumab on the eligibility for apheresis using predefined US and EU apheresis criteria. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to evinacumab 15 mg/kg intravenously every 4 weeks (Q4W; n=43) or placebo (n=22). We assessed the proportion of patients who met per protocol US apheresis criteria (LDL-C ≥300 mg/dL), newer US criteria for FH (LDL-C ≥300 mg/dL or LDL-C ≥160 mg/dL with coronary heart disease or peripheral artery disease) and per protocol EU apheresis criteria (LDL-C >160 mg/dL [primary prevention] or >120 mg/dL [secondary prevention]) at baseline and week 24. Results: Under the newer US criteria (2018), 62.8% (n=27) of evinacumab-treated patients and 54.5% (n=12) placebo-treated patients qualified for apheresis at baseline (Table). Following 24 weeks of treatment, 48.8% of all evinacumab versus 9.1% of all placebo patients no longer qualified for apheresis. Similar results were observed using EU apheresis criteria, where 46.5% of evinacumab-treated patients shifted from qualifying for apheresis at baseline to not qualifying at week 24, compared with 4.5% of placebo-treated patients. The majority of evinacumab (65.1%) and placebo (68.2%) patients did not qualify for per protocol US apheresis at baseline, however a shift of 27.9% and 9.1% was observed, respectively. Conclusions: Evinacumab has the potential to reduce the need for apheresis in patients with HoFH.

scholarly journals Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors

2021 ◽  
Vol 23 (12) ◽  
Author(s):  
Angela Pirillo ◽  
Alberico L. Catapano ◽  
Giuseppe D. Norata
Keyword(s):  
Monoclonal Antibodies ◽  
High Risk ◽  
Familial Hypercholesterolemia ◽  
Plasma Levels ◽  
Low Density Lipoprotein ◽  
Genetic Defect ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Premature Cardiovascular Disease

Abstract Purpose of Review Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action. As most cases of FH are attributable to mutations in the gene encoding the low-density lipoprotein receptor (LDLR), statins, even in combination with ezetimibe, are less effective in reducing LDL-C plasma levels in FH patients, who require a more intensive approach with additional lipid-lowering agents. Additional targets playing key roles in regulating LDL-C levels are represented by PCSK9 and ANGPTL3. Recent Findings Two monoclonal antibodies (mAbs) targeting PCSK9, evolocumab and alirocumab, significantly reduce LDL-C levels in HeFH patients. In patients with HoFH, the efficacy of mAbs to PCSK9 is strictly related to the presence of a residual LDLR activity; thus, patients carrying null mutations do not respond to the therapy with these mAbs, whereas some effects can be appreciated in HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its LDLR-independent mechanism of action. Summary Monoclonal antibodies inhibiting PCSK9 have shown a robust effect in FH patients presenting a residual LDLR activity, while ANGPTL3 inhibitors appear to be promising even in patients carrying null LDLR mutations.

scholarly journals Familial hypercholesterolemia: etiopathogenesis, diagnosis, treatment and state of the problem in Ukraine

2019 ◽  
Vol 26 (4) ◽  
pp. 23-31
Author(s):  
O. I. Mitchenko ◽  
V. Y. Romanov ◽  
N. M. Chulaevska ◽  
K. O. Timokhova
Keyword(s):  
Total Cholesterol ◽  
Familial Hypercholesterolemia ◽  
Cholesterol Level ◽  
Total Cholesterol Level ◽  
Genetic Disorders ◽  
Low Density Lipoprotein ◽  
Coronary Vessels ◽  
Density Lipoprotein ◽  
Epidemiological Data ◽  
Membrane Receptors

Familial hypercholesterolemia (FH) is one of the most common, inherited autosomal dominant diseases. Most often, FH is caused by dominant mutation of the gene, responsible for the synthesis of low density lipoprotein (LDL) membrane receptors that remove LDL from the blood plasma. As a result, individuals with a mutation of this gene from birth have a significantly increased level of cholesterol LDL in the blood. FH mediates the accelerated development of cardiovascular disease of atherosclerotic genesis, especially coronary heart disease (CHD), so the level of cardiovascular mortality in the population of such patients is extremely high. The article focuses on the fact that the main threat of these lipid disorders is the early and rapid initiation of atherosclerotic lesions of coronary vessels: in patients with heterozygous FH with a total cholesterol level of 8–15 mmol/l, CHD usually manifests up to 55 and 60 years, whereas in homozygous patients with a total cholesterol level of 12–30 mmol/l, CHD manifests at the start of their life and if left untreated, death occurs by the age of 20 years. The major genetic disorders in familial hypercholesterolemia and the frequency of their detection in the population are characterized. There are definitions of clinical screening options for FH: targeted, opportunistic, universal, cascadic. A comprehensive view of the diagnosis of FH according to the Dutch Lipid Clinic Network (DLCN) is provided. The basic principles of non-medication and three-step medication treatment of FH are presented. The article presents a clinical case of the homozygous FH taking into account the peculiarities of the disease course, the results of laboratory and instrumental studies and step-by-step treatment in the department of dyslipidemia of M.D. Strazhesko Institute of Cardiology of NAMS of Ukraine. The epidemiological data of the Ukrainian population survey on the possible prevalence of FH in Ukraine are presented. The preliminary analysis of the Ukrainian registry of patients with FH as a national fragment of the international ScreenProFH Registry and the European Register EAS-FHSC is provided.

Plasma homocyst(e)ine as a risk factor for early familial coronary artery disease

1994 ◽  
Vol 40 (4) ◽  
pp. 552-561 ◽  
Author(s):  
L L Wu ◽  
J Wu ◽  
S C Hunt ◽  
B C James ◽  
G M Vincent ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coronary Risk Factors ◽  
Low Density Lipoprotein Cholesterol ◽  
Relative Odds ◽  
The Mean ◽  
High Concentrations ◽  
Artery Disease

Abstract We measured plasma homocyst(e)ine [H(e)] and other coronary risk factors in 266 patients with early coronary artery disease from 170 families in which two or more siblings were affected and in 168 unmatched controls. The mean H(e) concentration adjusted for significant correlates (serum creatinine, uric acid, and low-density lipoprotein cholesterol) was 12.0 mumol/L in proband cases compared with 10.1 mumol/L in controls (P = 0.0001). Many (17.6%) of the proband cases had H(e) concentrations exceeding the 95th percentile for the controls (relative odds = 4.9, P &lt; 0.001). H(e) among cases was bimodally distributed even after adjustment for concentrations of plasma vitamins. Concordant high H(e) was seen in at least 10 (12%) of 85 families with two or more affected siblings. We conclude that a substantial proportion of early familial coronary artery disease is probably related to production of high concentrations of H(e) by one or more major genes.

scholarly journals Does Nut Consumption Reduce Mortality and/or Risk of Cardiometabolic Disease? An Updated Review Based on Meta-Analyses

2019 ◽  
Vol 16 (24) ◽  
pp. 4957 ◽  
Author(s):  
Yoona Kim ◽  
Jennifer B Keogh ◽  
Peter M Clifton
Keyword(s):  
Total Cholesterol ◽  
Fasting Glucose ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cochrane Library ◽  
Cardiometabolic Disease ◽  
Stroke Incidence ◽  
Glucose Levels ◽  
Artery Disease ◽  
Meta Analyses

Aim We aimed to determine if nut consumption decreases mortality and/or the risk of cardiometabolic diseases based on updated meta-analyses of epidemiological and intervention studies. Methods. An updated electronic search was conducted in PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library databases for original meta-analyses to investigate the effects of nut consumption on cardiometabolic disease in humans. Results. Seven new meta-analyses were included in this updated review. Findings similar to our previous review were observed, showing that nut consumption significantly decreased cardiovascular disease (CVD) mortality (−19% to −25%; n = 4), coronary heart disease (CHD) mortality (−24% to −30%; n = 3), stroke mortality (−17% to −18%; n = 3), CVD incidence (−15% to −19 %; n = 4), CHD [or coronary artery disease (CAD)] incidence (−17% to −34%; n = 8), and stroke incidence (−10% to −11%; n = 6) comparing high with low categories of nut consumption. Fasting glucose levels (0.08 to 0.15 mmol/L; n = 6), total cholesterol (TC; 0.021 to 0.30 mmol/L; n = 10), and low-density lipoprotein cholesterol (LDL-C; 0.017 to 0.26 mmol/L; n = 10) were significantly decreased with nut consumption compared with control diets. Body weight and blood pressure were not significantly affected by nut consumption. Conclusion. Nut consumption appears to exert a protective effect on cardiometabolic disease, possibly through improved concentrations of fasting glucose, total cholesterol, and LDL-C.

Secondary prevention care and effect: Total and low-density lipoprotein cholesterol levels and lipid-lowering drug use in women and men after incident myocardial infarction – The Tromsø Study 1994–2016

2018 ◽  
Vol 17 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Laila A Hopstock ◽  
Anne Elise Eggen ◽  
Maja-Lisa Løchen ◽  
Ellisiv B Mathiesen ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Lipid Levels ◽  
Treatment Target ◽  
Cholesterol Levels ◽  
Lipid Lowering Drug ◽  
Lowering Drug

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994–1995 and 8483 participants (55% women) attending the Tromsø Study 2007–2008 for first-ever MI up to their participation in 2007–2008 and 2015–2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994–2008 and 2007–2013, respectively. Mean change in total cholesterol was −2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was −1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was −0.33 (95% confidence interval [CI] −0.51 to −0.14) for total cholesterol and −0.21 (95% CI −0.37 to −0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15−2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.

No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia

2015 ◽  
Vol 30 (1) ◽  
Author(s):  
Georgia Ragia ◽  
Vana Kolovou ◽  
Anna Tavridou ◽  
Laure Elens ◽  
Alexandros D. Tselepis ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Genetic Factors ◽  
Interindividual Variability ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Primary Hypercholesterolemia ◽  
Entire Cohort

AbstractInterindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors.A total of 416 statin-treated (207 atorvastatin- and 209 simvastatin-treated) adults with primary hypercholesterolemia were included in the study. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment.In the entire cohort population, 41 individuals carriedThe effect of

scholarly journals Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia

2005 ◽  
Vol 153 (5) ◽  
pp. 679-686 ◽  
Author(s):  
Cheng-Chieh Lin ◽  
Tsai-Chung Li ◽  
Ming-May Lai
Keyword(s):  
Total Cholesterol ◽  
Apolipoprotein B ◽  
Clinical Laboratory ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Monascus Purpureus ◽  
Lipid Lowering ◽  
Controlled Study ◽  
Double Blind

Objective: The purpose of this study was to assess the lipid-lowering effect of Monascus purpureus Went rice on serum lipids in patients with hyperlipidemia, and to assess its safety by reporting adverse events and clinical laboratory measurements. Design and methods: This was a randomized, double-blind, placebo-controlled study. In all, 79 patients (aged 23–65 years) with a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 5.28 mmol/l (203.9 mg/dl) received a twice daily dose of placebo or Monascus purpureus Went rice (600 mg) for 8 weeks. Results: At week 8, Monascus purpureus Went rice therapy reduced LDL-C by 27.7%, total cholesterol by 21.5%, triglycerides by 15.8% and apolipoprotein B by 26.0%. High-density lipoprotein cholesterol and apolipoprotein A-I levels were increased by 0.9 and 3.4% respectively (not significant). No patient in the Monascus purpureus Went rice treatment group had an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatine phosphokinase (CPK) measurement that was ≥ 3 times the upper limit of normal at week 4 and week 8. Conclusion: Monascus purpureus Went rice significantly reduced LDL-C, total cholesterol, triglycerides and apolipoprotein B levels, and was well tolerated in patients with hyperlipidemia. However, this study only provides data from an 8-week trial and long-term safety and efficacy data are needed.

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