scholarly journals Prevalence and Impact of Apolipoprotein E7 on LDL Cholesterol Among Patients With Familial Hypercholesterolemia

2021 ◽  
Vol 8 ◽  
Author(s):  
Hayato Tada ◽  
Kan Yamagami ◽  
Nobuko Kojima ◽  
Junichi Shibayama ◽  
Tetsuo Nishikawa ◽  
...  
Keyword(s):  
General Population ◽  
Familial Hypercholesterolemia ◽  
Serum Lipids ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pathogenic Mutation ◽  
Lipid Levels ◽  
Coding Regions ◽  
Cholesterol Levels

Background: It has been suggested that a rare mutant apolipoprotein E7, APOE7 (p.Glu262Lys, p.Glu263Lys), has been identified to be associated with hyperlipoproteinemia in the general population. Moreover, its prevalence has been shown to be 0.005–0.06%. However, there are no prior data regarding its prevalence and impact on serum lipids in patients with familial hypercholesterolemia (FH).Methods: We recruited 1,138 patients with clinically diagnosed FH [mean age = 48, men = 512, median low-density lipoprotein (LDL) cholesterol = 231 mg/dl]. The coding regions of three FH genes (LDLR, APOB, and PCSK9) and apolipoprotein E (APOE) gene were sequenced. We investigated the prevalence and impact of APOE7 mutant on serum lipid levels in patients with FH.Results: We identified 29 patients (2.5 %) with a mutant APOE7 (heterozygote), which is apparently much higher than that of the general population. Moreover, when we focus on those without FH mutation (n = 540), we identified 21 patients (3.9 %) with a mutant APOE7. Patients with a mutant APOE7 exhibited significantly higher median LDL cholesterol and triglyceride levels compared with those without this rare mutant (249 vs. 218 mg/dl, p < 0.05, 216 vs. 164 mg/dl, p < 0.05, respectively). Moreover, LDL cholesterol levels in the APOE7-oligogenic FH individuals, with a pathogenic mutation in FH genes and APOE7 mutant, were significantly higher than that in monogenic FH patients (265 vs. 245 mg/dl, p < 0.05).Conclusion: We identified more patients with a mutant APOE7 than expected among those diagnosed with FH clinically, especially among those without FH-causing mutation. This implies a mutant APOE7 may be one of the causes FH, especially among those without FH mutations.

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.

Lipid Levels in Schoolchildren in North East England: Effects of Feeding and Age

1994 ◽  
Vol 31 (3) ◽  
pp. 233-239 ◽  
Author(s):  
K Azad ◽  
S Court ◽  
J M Parkin ◽  
M F Laker ◽  
K G M M Alberti
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Lipid Levels ◽  
North East ◽  
Cholesterol Levels ◽  
Log Normal ◽  
Effect Of Feeding

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein (apo) A-I and apoB concentrations were estimated and low-density lipoprotein (LDL) cholesterol levels were calculated in 132 children aged 11·4–17·3 years. The effect of feeding was investigated by estimating postprandial values and also by studying the effects of a test meal. The distribution of all data was consistent with Gaussian apart from triglycerides which was log normal. Overall fasting values were [mean (standard deviation; SD)] cholesterol 4·5 (0·8) mmol/L, HDL cholesterol 1·5 (0·4) mmol/L, LDL cholesterol 2·6 (0·8) mmol/L, apoA-I 1·5 (0·3) g/L, apoB 1·0 (0·4) g/L and triglycerides 0·76 (0·38–1·51) mmol/L, the values for triglycerides being mean (95% confidence intervals). Girls had higher triglycerides than boys [0·82 (0·43–1·54) versus 0·70 (0·36–1·33)] and different effects of age on lipids were found, HDL cholesterol being negatively correlated with age in boys ( r= −0·37; P<0·001), but not in girls, and apoA-I being negatively correlated with age in boys ( r= −0·31; P=0·006), but positively correlated with age in girls ( r = 0·32; P = 0·008). Triglycerides rose and HDL cholesterol fell following feeding and inconsistent effects were seen on apoA-I and apoB.

scholarly journals Familial Hypercholesterolemia: Do HDL Play a Role?

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 810
Author(s):  
Juan Pedro-Botet ◽  
Elisenda Climent ◽  
David Benaiges
Keyword(s):  
Familial Hypercholesterolemia ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Human Metabolism ◽  
High Cardiovascular Risk ◽  
Monogenic Disorder ◽  
Cholesterol Levels

Cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (HeFH), the most frequent monogenic disorder of human metabolism, is largely driven by low-density lipoprotein (LDL) cholesterol concentrations. Since the CVD rate differs considerably in this population, beyond the lifetime LDL cholesterol vascular accumulation, other classical risk factors are involved in the high cardiovascular risk of HeFH. Among other lipoprotein disturbances, alterations in the phenotype and functionality of high-density lipoproteins (HDL) have been described in HeFH patients, contributing to the presence and severity of CVD. In fact, HDL are the first defensive barrier against the burden of high LDL cholesterol levels owing to their contribution to reverse cholesterol transport as well as their antioxidant and anti-inflammatory properties, among others. In this context, the present narrative review aimed to focus on quantitative and qualitative abnormalities in HDL particles in HeFH, encompassing metabolic, genetic and epigenetic aspects.

Effect of ascorbate on serum lipids and urate metabolism during exhaustive training

2004 ◽  
Vol 106 (1) ◽  
pp. 107-109 ◽  
Author(s):  
Hidekatsu YANAI ◽  
Mie MORIMOTO
Keyword(s):  
Placebo Group ◽  
Serum Lipids ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serum Urate ◽  
Exhaustive Exercise ◽  
Controlled Study ◽  
Cholesterol Levels

Physical activity is associated with beneficial changes in serum lipids, but exhaustive exercise has been suggested to increase oxidative stress. To test the effect of ascorbate (vitamin C) on serum lipids and the metabolism of urate, which is the most important intrinsic antioxidant, during exhaustive exercise, we performed a randomized, blinded, placebo-controlled study on eight male well-trained athletes. subjects were randomly allocated to either a group given 1000 mg of ascorbate daily (n=4) or a placebo group (n=4). Fasting serum lipids and urate concentrations were measured before and after 3 weeks of training. Although serum low-density lipoprotein (LDL)-cholesterol levels decreased and high-density lipoprotein (HDL)-cholesterol levels increased significantly in the ascorbate group after the 3 weeks of training, serum LDL-cholesterol levels increased and HDL-cholesterol levels decreased significantly in the placebo group. Furthermore, serum urate levels were elevated significantly in the placebo group; however, these levels did not change in the ascorbate group. When compared with the placebo group, significantly higher serum HDL-cholesterol and lower serum LDL-cholesterol and urate levels were observed in the ascorbate group after training. In conclusion, our results suggested that ascorbate may contribute to the desirable changes in serum lipids during exhaustive training and suggest the significant association between ascorbate and urate under intense training.

Therapy of Familial Hypercholesterolemia in Childhood: Diet and Cholestyramine Resin for 24 to 36 Months

PEDIATRICS ◽  
1977 ◽  
Vol 59 (3) ◽  
pp. 433-441
Author(s):  
C. J. Glueck ◽  
R. C. Tsang ◽  
R. W. Fallat ◽  
M. Mellies
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cholesterol Level ◽  
Ldl Cholesterol ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Cholesterol Level ◽  
Drug Adherence ◽  
Cholesterol Levels ◽  
Childhood Diet

In 16 children heterozygous for familial hypercholesterolemia, two- to three-year therapy with diet and cholestyramine resin (16 gm/day) was assessed in terms of effectiveness, practicality, and safety. All 16 children had previously taken a low-cholesterol (&lt; 300 mg/day), polyunsaturate-rich (P/S ratio, 1.5:1) diet and cholestyramine resin (12 gm/day) for 12 months. In this study, the cholestyramine resin dose was increased to 16 gm/day, and follow-up was maintained through months 13 through 18, 19 through 24, 25 through 30, and 31 through 36. Eleven children had good drug adherence (four packs of cholestyramine per day) and five children had fair adherence (two to three packs per day). Plasma total cholesterol and low-density lipoprotein (LDL) cholesterol levels were not significantly lowered on the drug-plus-diet regimen as compared to diet alone in five children with fair drug adherence. For children with good drug adherence. mean plasma cholesterol level was lowered below levels achieved on diet alone by 13% (months 13 through 18), 12% (months 19 through 24), 12% (months 25 through 30), and 11% (months 31 through 36) (P &lt; .05). Reduction in plasma cholesterol level was no greater with 16 than with 12 gm of cholestyramine per day. There were no group changes in mean plasma triglyceride levels. Cholestyramine resin, when added to diet and maintained for two to three years, effects a significant reduction in total and LDL cholesterol levels in about 60% of children heterozygous for familial hypercholesterolemia. Continued reinforcelnent of both diet and drug adherence is necessary in the face of gradual increments in plasma cholesterol level with time.

scholarly journals Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD)

2021 ◽  
Vol 10 (14) ◽  
pp. 3098
Author(s):  
Shota Okutsu ◽  
Yoshifumi Kato ◽  
Shunsuke Funakoshi ◽  
Toshiki Maeda ◽  
Chikara Yoshimura ◽  
...  
Keyword(s):  
Weight Gain ◽  
General Population ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Population Based ◽  
Lipid Lowering ◽  
Low Density ◽  
Obesity Hypertension ◽  
Old Men

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

scholarly journals The LDLR, APOB, and PCSK9 Variants of Index Patients with Familial Hypercholesterolemia in Russia

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 66
Author(s):  
Alexey Meshkov ◽  
Alexandra Ershova ◽  
Anna Kiseleva ◽  
Evgenia Zotova ◽  
Evgeniia Sotnikova ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Significant Proportion ◽  
Density Lipoprotein ◽  
Genetic Diagnostics ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gene Variants ◽  
Systematic Analysis ◽  
Pcsk9 Gene ◽  
Cholesterol Levels

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of LDLR, APOB, and PCSK9 genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood. The aim of this study is to present data on the spectrum of LDLR, APOB, and PCSK9 gene variants in a cohort of 595 index Russian patients with FH, as well as an additional systematic analysis of the literature for the period of 1995–2020 on LDLR, APOB and PCSK9 gene variants described in Russian patients with FH. We used targeted and whole genome sequencing to search for variants. Accordingly, when combining our novel data and the data of a systematic literature review, we described 224 variants: 187 variants in LDLR, 14 variants in APOB, and 23 variants in PCSK9. A significant proportion of variants, 81 of 224 (36.1%), were not described earlier in FH patients in other populations and may be specific for Russia. Thus, this study significantly supplements knowledge about the spectrum of variants causing FH in Russia and may contribute to a wider implementation of genetic diagnostics in FH patients in Russia.

Abstract P307: Chitin-Glucan Fiber Effects on Oxidized Low-Density Lipoprotein: A Randomized Controlled Trial

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Joseph L Evans ◽  
Harold Bays ◽  
Kevin C Maki ◽  
Mal Evans ◽  
Veronique Maquet ◽  
...  
Keyword(s):  
Diabetes Complications ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Secondary Outcome ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Treatment Groups ◽  
Cholesterol Levels ◽  
Insoluble Fiber

Oxidized low-density lipoprotein (OxLDL) is believed to play a role in the progression of atherosclerotic coronary heart disease (CHD) and the development of diabetes complications. This randomized, double-blind, placebo-controlled study of a novel insoluble fiber derived from the mycelium Aspergillus niger , chitin-glucan (CG) (ARTINIA™), evaluated 135 patients with fasting LDL-cholesterol 130-189.9 mg/dl and fasting glucose <=125 mg/dl. Participants were randomly assigned to receive CG (4.5 g/day; n=34), CG (1.5 g/day; n=33), CG (1.5 g/day) plus olive extract (n=33), or matching placebo (n=35) for 6 weeks. The primary outcome measure was the between-group difference in OxLDL. Secondary outcome measurements included effects upon lipid, glucose, insulin, and F2-isoprostane levels. After 6 weeks, CG 4.5 g/day (CG-4.5) significantly reduced mean OxLDL 3.8 U/L compared to baseline (58.0 U/L vs 61.8 U/L, respectively; P =0.006), and reduced OxLDL 4.97 U/L compared to placebo (P=<0.05). Other treatment groups generally had no significant effect upon OxLDL. CG treatment groups reduced LDL-cholesterol levels 3.2–;6.5% compared to placebo (P<0.05). In this study population without diabetes mellitus or elevated glucose levels, CG did not significantly affect high density lipoprotein cholesterol, triglycerides, glucose, insulin, F2-isoprostanes, or the homeostasis model assessment of insulin resistance. Treatments were well tolerated and with adverse experiences comparable to placebo. These results suggest that chitin-glucan, a novel insoluble fiber, may significantly reduce OxLDL and LDL-cholesterol levels, which may have therapeutic implications for patients at risk for CHD or other diabetes complications.

scholarly journals Pharmacokinetics, Distribution in Serum Lipoproteins and Tissues, and Renal Toxicities of Amphotericin B and Amphotericin B Lipid Complex in a Hypercholesterolemic Rabbit Model: Single-Dose Studies

1998 ◽  
Vol 42 (12) ◽  
pp. 3146-3152 ◽  
Author(s):  
Kishor M. Wasan ◽  
Allison L. Kennedy ◽  
Shawn M. Cassidy ◽  
Manisha Ramaswamy ◽  
Lorilynne Holtorf ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Ldl Cholesterol ◽  
Renal Toxicity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Total Serum ◽  
Lipid Complex ◽  
Blood Samples ◽  
Regular Diet ◽  
Cholesterol Levels

ABSTRACT The purpose of this study was to determine if a relationship exists among total serum and lipoprotein cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the serum pharmacokinetics of AmpB in hypercholesterolemic rabbits administered AmpB and AmpB lipid complex (ABLC). After 10 days of cholesterol-enriched diet (0.50% [wt/vol]) or regular rabbit diet (control), each rabbit was administered a single intravenous bolus of AmpB or ABLC (1.0 mg/kg of body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, kidney toxicity, and serum lipoprotein distribution. Rabbits were humanely sacrificed after all blood samples were obtained, and tissues were harvested for drug analysis. Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total serum cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with levels in rabbits on a regular diet. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered AmpB. However, the magnitude of this increase was 2.5-fold greater in cholesterol-fed rabbits than in regular diet-fed rabbits. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered ABLC. Whereas AmpB pharmacokinetics were significantly altered in cholesterol-fed rabbits administered free AmpB, similar AmpB pharmacokinetics were observed in both rabbit groups administered ABLC. Renal AmpB levels were significantly increased in cholesterol-fed rabbits administered AmpB compared with those in all other groups. Hepatic and lung AmpB levels were elevated in cholesterol-fed rabbits administered free AmpB compared to controls. In addition, hepatic, lung, and spleen AmpB levels were significantly decreased in cholesterol-fed rabbits administered ABLC compared to controls. An increased percentage of AmpB was recovered in LDL–very-low-density lipoprotein fraction when free AmpB was administered to cholesterol-fed rabbits compared with those in all other groups. These findings suggest that increases in cholesterol, specifically, LDL cholesterol levels, modify the disposition and renal toxicity of free AmpB. However, the pharmacokinetics and renal toxicity of ABLC were independent of elevations in total and LDL cholesterol levels.

Dyslipidaemia

2019 ◽  
pp. 33-48
Author(s):  
Heinz Drexel
Keyword(s):  
Cardiovascular Disease ◽  
Randomized Clinical Trials ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Epidemiological Studies ◽  
Residual Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cholesterol Levels

Lipid metabolism has gained cardiological interest only after statins were demonstrated to reduce cardiovascular disease in secondary and primary prevention. Therefore, this chapter first introduces the physiological and atherogenic properties of lipoproteins, before focusing on interventions. Both the efficacy and safety of statins have been proven in numerous randomized clinical trials. Because there is a considerable residual risk in statin-treated patients, additional approaches have been investigated. The focus is now on further reductions in low-density lipoprotein (LDL) cholesterol levels. First, high-intensity statin regimens were shown to reduce residual risk. Subsequently, ezetimibe was demonstrated, for the first time, to have a beneficial effect as a non-statin lipid intervention. More recently, inhibitors of the enzyme PCSK9 have demonstrated a very high efficacy in reducing LDL cholesterol levels. Although the causality of LDL for atherosclerotic cardiovascular disease has been proven in epidemiological studies, including Mendelian randomization studies, as well as interventional trials, adherence to statins and other therapies is far from optimal. In contrast, interventions to increase high-density lipoprotein (HDL) cholesterol levels could not proven to have further benefits when combined with statins.

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