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HPS2-THRIVE, AIM-HIGH and dal-OUTCOMES: HDL-cholesterol under attack.

Hassan M - Glob Cardiol Sci Pract (2014)

View Article: PubMed Central - PubMed

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A low level of high-density lipoprotein cholesterol (HDL-C) is an established predictor of the risk of coronary heart disease (CHD)... A linear inverse relation has been reported in many observational studies between plasma HDL-C level and incident CHD events, with a plateau effect at HDL-C values >90 mg/dL in men and 75 mg/dL in women... However, it remains uncertain whether raising HDL-C levels therapeutically (by either niacin or cholesterol ester transfer protein “CETP” inhibitors) would reduce subsequent cardiovascular (CV) events beyond that achieved with intensive statin therapy... Over a median follow up period of 3.9 years, HDL-C levels increased by 6 mg/dL, triglycerides levels decreased by 33 mg/dL, and LDL-C levels decreased by 10 mg/dL in the niacin-laropiprant group... This study was designed to test whether extended-release niacin added to intensive statin therapy, as compared to statin therapy alone, would reduce the risk of CV events in patients with established atherosclerotic CV disease (defined as stable coronary, cerebrovascular or peripheral arterial disease) and atherogenic dyslipidemia (low baseline levels of HDL-C < 40 mg/dL for men; < 50 mg/dL for women, and elevated triglyceride levels 150 to 400 mg/dL)... Over a follow up period of 31 months, HDL-C levels substantially increased by 31 to 40% in the dalcetrapib group and by 4 to 11% in the placebo group with minimal effect on LDL-C and fasting blood glucose levels... Dalcetrapib had no significant effect on the primary end-point, as compared to placebo (8.3% vs 8.0% respectively, hazard ratio with dalcetrapib, 1.04; 95% CI, 0.93–1.16; p = 0.52)... It is worth mentioning that patients in all studies were pre-treated with high intensity statin therapy that made baseline lipid profile was relatively normal before randomization... Of note, in the original Coronary Drug Project, before the statin era, high dose immediate release niacin was associated with a significant reduction (14%) in the rate of death from CHD or MI and a reduction (26%) in the rate of strokes or transient ischemic attacks... In the HPS2-THRIVE study, average baseline LDL-C was 63 mg/dL, HDL-C was 44 mg/dL, and triglycerides was125 mg/dL before study drug treatment... Of further concern, major vascular event reduction in the niacin-laropiprant group was strongly predicted by baseline LDL-C (p = 0.02), with apparent clinical benefit if baseline LDL-C level was above 58 mg/dL... It is uncertain whether HDL-C is a causal risk factor or a risk marker... We are looking forward the results of ACCELERATE and REVEAL studies in order to have a final conclusion... Ultimately, new therapeutic targets should be investigated such as lowering apoC3 which has been shown to significantly reduce plasma levels of triglycerides and increase HDL-C level... Interestingly, loss of function mutation of apoC3 has been recently reported to be associated with reduced risk of CHD.

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Related in: MedlinePlus

Reverse Cholesterol Transport. ABCA1, ATP binding cassette A1 transporter; ABCG1, ATP binding cassette G1 transporter; CETP, cholesterol ester transfer protein; SR-B1: Scavenger receptor-B1; LDLR, low density lipoprotein receptor.
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Related In: Results  -  Collection


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fig1: Reverse Cholesterol Transport. ABCA1, ATP binding cassette A1 transporter; ABCG1, ATP binding cassette G1 transporter; CETP, cholesterol ester transfer protein; SR-B1: Scavenger receptor-B1; LDLR, low density lipoprotein receptor.

Mentions: A low level of high-density lipoprotein cholesterol (HDL-C) is an established predictor of the risk of coronary heart disease (CHD).1 HDL promotes cellular cholesterol efflux and reverse cholesterol transport from lipid-laden macrophages (Figure 1), and prevents lipoprotein oxidation. A linear inverse relation has been reported in many observational studies between plasma HDL-C level and incident CHD events, with a plateau effect at HDL-C values >90 mg/dL in men and 75 mg/dL in women.2 However, it remains uncertain whether raising HDL-C levels therapeutically (by either niacin or cholesterol ester transfer protein “CETP” inhibitors) would reduce subsequent cardiovascular (CV) events beyond that achieved with intensive statin therapy.


HPS2-THRIVE, AIM-HIGH and dal-OUTCOMES: HDL-cholesterol under attack.

Hassan M - Glob Cardiol Sci Pract (2014)

Reverse Cholesterol Transport. ABCA1, ATP binding cassette A1 transporter; ABCG1, ATP binding cassette G1 transporter; CETP, cholesterol ester transfer protein; SR-B1: Scavenger receptor-B1; LDLR, low density lipoprotein receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352676&req=5

fig1: Reverse Cholesterol Transport. ABCA1, ATP binding cassette A1 transporter; ABCG1, ATP binding cassette G1 transporter; CETP, cholesterol ester transfer protein; SR-B1: Scavenger receptor-B1; LDLR, low density lipoprotein receptor.
Mentions: A low level of high-density lipoprotein cholesterol (HDL-C) is an established predictor of the risk of coronary heart disease (CHD).1 HDL promotes cellular cholesterol efflux and reverse cholesterol transport from lipid-laden macrophages (Figure 1), and prevents lipoprotein oxidation. A linear inverse relation has been reported in many observational studies between plasma HDL-C level and incident CHD events, with a plateau effect at HDL-C values >90 mg/dL in men and 75 mg/dL in women.2 However, it remains uncertain whether raising HDL-C levels therapeutically (by either niacin or cholesterol ester transfer protein “CETP” inhibitors) would reduce subsequent cardiovascular (CV) events beyond that achieved with intensive statin therapy.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

A low level of high-density lipoprotein cholesterol (HDL-C) is an established predictor of the risk of coronary heart disease (CHD)... A linear inverse relation has been reported in many observational studies between plasma HDL-C level and incident CHD events, with a plateau effect at HDL-C values >90 mg/dL in men and 75 mg/dL in women... However, it remains uncertain whether raising HDL-C levels therapeutically (by either niacin or cholesterol ester transfer protein “CETP” inhibitors) would reduce subsequent cardiovascular (CV) events beyond that achieved with intensive statin therapy... Over a median follow up period of 3.9 years, HDL-C levels increased by 6 mg/dL, triglycerides levels decreased by 33 mg/dL, and LDL-C levels decreased by 10 mg/dL in the niacin-laropiprant group... This study was designed to test whether extended-release niacin added to intensive statin therapy, as compared to statin therapy alone, would reduce the risk of CV events in patients with established atherosclerotic CV disease (defined as stable coronary, cerebrovascular or peripheral arterial disease) and atherogenic dyslipidemia (low baseline levels of HDL-C < 40 mg/dL for men; < 50 mg/dL for women, and elevated triglyceride levels 150 to 400 mg/dL)... Over a follow up period of 31 months, HDL-C levels substantially increased by 31 to 40% in the dalcetrapib group and by 4 to 11% in the placebo group with minimal effect on LDL-C and fasting blood glucose levels... Dalcetrapib had no significant effect on the primary end-point, as compared to placebo (8.3% vs 8.0% respectively, hazard ratio with dalcetrapib, 1.04; 95% CI, 0.93–1.16; p = 0.52)... It is worth mentioning that patients in all studies were pre-treated with high intensity statin therapy that made baseline lipid profile was relatively normal before randomization... Of note, in the original Coronary Drug Project, before the statin era, high dose immediate release niacin was associated with a significant reduction (14%) in the rate of death from CHD or MI and a reduction (26%) in the rate of strokes or transient ischemic attacks... In the HPS2-THRIVE study, average baseline LDL-C was 63 mg/dL, HDL-C was 44 mg/dL, and triglycerides was125 mg/dL before study drug treatment... Of further concern, major vascular event reduction in the niacin-laropiprant group was strongly predicted by baseline LDL-C (p = 0.02), with apparent clinical benefit if baseline LDL-C level was above 58 mg/dL... It is uncertain whether HDL-C is a causal risk factor or a risk marker... We are looking forward the results of ACCELERATE and REVEAL studies in order to have a final conclusion... Ultimately, new therapeutic targets should be investigated such as lowering apoC3 which has been shown to significantly reduce plasma levels of triglycerides and increase HDL-C level... Interestingly, loss of function mutation of apoC3 has been recently reported to be associated with reduced risk of CHD.

No MeSH data available.


Related in: MedlinePlus