Effects of HDL-modifiers on cardiovascular outcomes: A meta-analysis of randomized trials

Verdoia, Monica; Schaffer, Alon; Suryapranata, Harry; Luca, Giuseppe De

doi:10.1016/j.numecd.2014.09.003

Cited by 31 publications

(22 citation statements)

References 69 publications

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“…A 2014 meta-analysis pooled clinical trials of niacin, fibrates, and CETP inhibitors involving a total of 117 411 patients and found no reduction in all-cause mortality, CHD, MI, or stroke [19 && ]. A 2015 metaanalysis of trials of niacin or CETP inhibitors involving 69 515 patients did not find a decrease in overall cardiovascular mortality [20].…”

Section: Doubts About the High Density Lipoprotein Hypothesismentioning

confidence: 96%

HDL-cholesterol and cardiovascular disease

Siddiqi

Kiss

Rader

2015

Current Opinion in Cardiology

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Section: Doubts About the High Density Lipoprotein Hypothesismentioning

confidence: 96%

HDL-cholesterol and cardiovascular disease

Siddiqi

Kiss

Rader

2015

Current Opinion in Cardiology

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“…The current study analyzed the HDL cholesterol turnover effect of NA using dual stable-isotope endogenous labeling of HDL-C and apoAI and modeling analysis. NA treatment had no effect on the I IS , which was measured in the present study because NA has been reported to increase the risk of diabetes onset [ 3 , 30 – 33 ]. In our study, we found that NA treatment improved reverse cholesterol transport (RCT) by increasing cholesterol esterification, HDL cholesterol disappearance through CETP independent pathways (i.e both endocytosis and selective uptake) and cell cholesterol efflux.…”

Section: Discussionmentioning

confidence: 64%

“…In humans, pharmacological doses of NA lead to reduction in plasma triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and an increase in high-density lipoprotein cholesterol (HDL-C). Epidemiological studies have suggested that this improvement in lipid profile can reduce the risk of coronary heart disease [ 2 ], through the HDL-C increase, but the recent findings of controlled outcome trials and meta-analyses have not fully supported this hypothesis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs

Bloch

Leray²,

Nazih³

et al. 2015

PLoS ONE

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AimNicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA) on lipids and high-density lipoprotein (HDL) cholesteryl ester (CE) turnover in obese Insulin-Resistant dogs with increase plasma triglycerides.MethodsHDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA-treated dogs was also measured.ResultsNA reduced plasma total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG), and very-low-density lipoprotein TG concentrations (p < 0.05). The kinetic study also showed a higher cholesterol esterification rate (p < 0.05). HDL-CE turnover was accelerated (p < 0.05) via HDL removal through endocytosis and selective CE uptake (p < 0.05). We measured an elevated in vitro cell cholesterol efflux (p < 0.05) with NA treatment in accordance with a higher cholesterol esterification.ConclusionNA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile.

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“…The failure of these three CETP inhibitors, along with the failed niacin trials, has led to major uncertainty about the benefit of raising HDL-C levels. Unsurprisingly, two meta-analyses of pooled clinical trials of HDL-raising drugs found no evidence of reduction in cardiovascular events or mortality (Keene et al, 2014;Verdoia et al, 2015).…”

Section: Cell Metabolismmentioning

confidence: 99%

New Therapeutic Approaches to the Treatment of Dyslipidemia

Rader

2016

Cell Metabolism

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Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease (ASCVD). Abundant data indicate that low-density lipoproteins (LDL) are causal for ASCVD; a new class of LDL-lowering medicines, the PCSK9 inhibitors, will address much unmet medical need. Human genetics suggest that triglyceride-rich lipoproteins (TRL) are pro-atherogenic and have pointed to a number of protein regulators of lipoprotein lipase activity that are candidates for therapeutic targeting. Finally, high-density lipoprotein (HDL) cholesterol does not appear to be causally associated with protection from ASCVD, reinforced by the failure of three CETP inhibitors in CV outcome trials, but HDL function remains of interest.

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Effects of HDL-modifiers on cardiovascular outcomes: A meta-analysis of randomized trials

Cited by 31 publications

References 69 publications

HDL-cholesterol and cardiovascular disease

HDL-cholesterol and cardiovascular disease

Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs

New Therapeutic Approaches to the Treatment of Dyslipidemia

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