LDL-cholesterol lowering and clinical outcomes in hypercholesterolemic subjects with and without a familial hypercholesterolemia phenotype: Analysis from the secondary prevention 4S trial

Background: Studies on the cholesterol lowering activity of tocotrienols have yielded mixed results, with some showing cholesterol lowering effect while some showing no activity.Aim: A randomized, double-blind, parallel group study was conducted to investigate the cholesterol lowering activity of tocotrienols. Methods: Thirty-two hypercholesterolemic subjects were randomly assigned to orally receive either 300 mg of mixed tocotrienols capsules daily or placebo capsules containing 300 mg of soya bean oil for a period of 6 months. The subjects were monitored before supplementation and monthly thereafter for their serum cholesterol as well as tocotrienol and tocopherol concentrations.Results: The serum total cholesterol and low density lipoprotein (LDL) cholesterol of the subjects in the tocotrienol supplementation group were decreased significantly by -8.9 ± 0.9% and -12.8 ± 2.6% respectively after 4 months of supplementation and the reduction persisted till the end of the 6-month study, with a reduction of -10.8 ± 1.0% and -17.3 ± 1.8%, respectively from baseline. Moreover, there was a 22-fold increase in the total tocotrienol concentrations from baseline during supplementation compared to the placebo group, while the concentration of α-tocopherol recorded only a modest increase. On the other hand, the serum cholesterol, total tocotrienol and α-tocopherol concentrations of subjects in the placebo group remained essentially unchanged.Conclusions: Supplementation with mixed tocotrienols at dose of 300 mg per day resulted in the lowering of the serum total and LDL cholesterol levels after 5 months of supplementation.Keywords: tocotrienols, cholesterol-lowering, total cholesterol, LDL cholesterol, tocopherols

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A Global Review on the Utility of Genetic Testing for Familial Hypercholesterolemia

Journal of Personalized Medicine ◽

10.3390/jpm10020023 ◽

2020 ◽

Vol 10 (2) ◽

pp. 23 ◽

Cited By ~ 2

Author(s):

Rachele M. Hendricks-Sturrup ◽

Jodi Clark-LoCascio ◽

Christine Y. Lu

Keyword(s):

United States ◽

Genetic Testing ◽

Familial Hypercholesterolemia ◽

Clinical Outcomes ◽

Ldl Cholesterol ◽

The United States ◽

Global Perspective ◽

Ongoing Research ◽

Increased Risk ◽

Patient Reported

Familial hypercholesterolemia (FH) is a genetic disorder of cholesterol metabolism that affects an estimated 1/250 persons in the United States and abroad. FH is hallmarked by high low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. This review summarizes recent global evidence showing the utility of FH genetic testing across diverse populations. Clinical and other qualitative outcomes following FH genetic testing were improved FH diagnosis, treatment initiation or continued treatment, treatment modification, improved total or LDL cholesterol levels, education on lifestyle management, and genetic counseling. This summary of evidence should be considered by those seeking overall evidence and knowledge gaps on the utility of FH genetic testing from a global perspective and for certain ethnic and age populations. These findings can be used to inform insurance policies and coverage decisions for FH genetic testing, policy recommendations to reduce the clinical and public health burden of FH, clinical practice and guidelines to improve the management of FH populations, and ongoing research involving FH genetic testing. We conclude that further investigations are needed to examine: (1) non-clinical outcomes following FH genetic testing; (2) patient-reported outcomes following FH genetic testing to convey patient experiences, values, and goals; and (3) clinical outcomes following FH genetic testing in non-Caucasian and pediatric populations in the United States and abroad.

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Management of Familial Hypercholesterolemia: Current Status and Future Perspectives

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa122 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

David T W Lui ◽

Alan C H Lee ◽

Kathryn C B Tan

Keyword(s):

Familial Hypercholesterolemia ◽

Ldl Cholesterol ◽

Genetic Disorder ◽

Lipid Lowering ◽

Current Status ◽

Atherosclerotic Cardiovascular Disease ◽

Inadequate Response ◽

Cholesterol Lowering ◽

Cholesterol Levels ◽

Pubmed Database

Abstract Familial hypercholesterolemia (FH) is the most common monogenic disorder associated with premature atherosclerotic cardiovascular disease. Early diagnosis and effective treatment can significantly improve prognosis. Recent advances in the field of lipid metabolism have shed light on the molecular defects in FH and new therapeutic options have emerged. A search of PubMed database up to March 2020 was performed for this review using the following keywords: “familial hypercholesterolemia,” “diagnosis,” “management,” “guideline,” “consensus,” “genetics,” “screening,” “lipid lowering agents.” The prevalence rate of heterozygous FH is approximately 1 in 200 to 250 and FH is underdiagnosed and undertreated in many parts of the world. Diagnostic criteria have been developed to aid the clinical diagnosis of FH. Genetic testing is now available but not widely used. Cascade screening is recommended to identify affected family members, and the benefits of early interventions are clear. Treatment strategy and target is currently based on low-density lipoprotein (LDL) cholesterol levels as the prognosis of FH largely depends on the magnitude of LDL cholesterol-lowering that can be achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment and are cost-effective. Addition of newer medications like PCSK9 inhibitors is able to further lower LDL cholesterol levels substantially, but the cost is high. Lipoprotein apheresis is indicated in homozygous FH or severe heterozygous FH patients with inadequate response to cholesterol-lowering therapies. In conclusion, FH is a common, treatable genetic disorder, and although our understanding of this disease has improved, many challenges still remain for its optimal management.

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Effect of intensive LDL cholesterol lowering with PCSK9 monoclonal antibodies on tendon xanthoma regression in familial hypercholesterolemia

Atherosclerosis ◽

10.1016/j.atherosclerosis.2017.06.009 ◽

2017 ◽

Vol 263 ◽

pp. 92-96 ◽

Cited By ~ 6

Author(s):

Ana M. Bea ◽

Sofia Perez-Calahorra ◽

Victoria Marco-Benedi ◽

Itziar Lamiquiz-Moneo ◽

Estibaliz Jarauta ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Familial Hypercholesterolemia ◽

Ldl Cholesterol ◽

Cholesterol Lowering ◽

Tendon Xanthoma

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Pravastatin in heterozygous familial hypercholesterolemia: Low-density lipoprotein (LDL) cholesterol-lowering effect and LDL receptor activity on skin fibroblasts

Metabolism ◽

10.1016/0026-0495(91)90132-g ◽

1991 ◽

Vol 40 (10) ◽

pp. 1074-1078 ◽

Cited By ~ 10

Author(s):

A. Gaddi ◽

M. Arca ◽

A. Ciarrocchi ◽

S. Fazio ◽

G. D'Alò ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Receptor Activity ◽

Low Density ◽

Cholesterol Lowering ◽

Heterozygous Familial Hypercholesterolemia ◽

Cholesterol Lowering Effect

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Cereal-Based Snack Bar with Added Plant Stanol Ester (Benecol®) Consumed between Meals Lowers Serum Total and LDL Cholesterol Effectively in Mildly to Moderately Hypercholesterolemic Subjects

Cholesterol ◽

10.1155/2018/1463628 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Essi Sarkkinen ◽

Mari Lyyra ◽

Sakari Nieminen ◽

Päivi Kuusisto ◽

Ingmar Wester

Keyword(s):

Ldl Cholesterol ◽

Hdl Cholesterol ◽

Double Blind ◽

Cholesterol Lowering ◽

Plant Stanol Ester ◽

Parallel Design ◽

Plant Stanol ◽

Habitual Diet ◽

Stanol Ester ◽

Hypercholesterolemic Subjects

The cholesterol-lowering effect of foods with added plant sterols or stanols consumed as snacks might be compromised. The purpose of this study was to confirm the cholesterol-lowering efficacy of a specially formulated cereal-based snack bar with added plant stanol ester (1.6 g plant stanols/day) when consumed between meals twice a day. In a double-blind, placebo-controlled, 4-week parallel-design study, 71 mildly to moderately hypercholesterolemic subjects were randomized into one of two groups, stanol or placebo group. Subjects were advised to replace their ordinary snacks with test products in an isocaloric manner and otherwise keep their habitual diet unchanged. The study showed that a snack bar product with added plant stanol ester lowered LDL and non-HDL cholesterol by 8.6% and 9.2% (mean%-change), respectively, as compared to the placebo product. The change in LDL cholesterol was statistically significantly different (P=0.001) between the groups while the change in HDL cholesterol or triglycerides did not differ between the groups. In conclusion, the cereal-based snack bar with added plant stanol ester ingested without a meal reduced LDL cholesterol significantly without affecting HDL cholesterol or triglyceride concentrations in mildly hypercholesterolemic men and women. The study is registered as NCT03284918.

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