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Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.

Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Nordestgaard BG, Ray KK, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A, Watts GF, European Atherosclerosis Society Consensus Pan - Eur. Heart J. (2011)

Bottom Line: If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered.Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates.These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

View Article: PubMed Central - PubMed

Affiliation: European Atherosclerosis Society, INSERM UMR-S939, Pitié-Salpetriere University Hospital, Paris 75651, France. john.chapman@upmc.fr

ABSTRACT
Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥ 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

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Lipoprotein cholesterol as a function of increasing levels of non-fasting triglycerides in the general population. Based on non-fasting samples from 36 160 men and women from the Copenhagen General Population Study collected over the period 2003–2007; 9% of men and 6% of women were on statins, mainly 40 mg/day simvastatin. Remnant cholesterol is calculated from a non-fasting lipid profile as total cholesterol minus HDL cholesterol minus LDL cholesterol; under these conditions, remnant cholesterol represents the total cholesterol transported in IDL, VLDL, and chylomicron remnants. Variable levels of chylomicrons are present in non-fasting samples and usually will only contribute minimally to the calculated remnant cholesterol. Nordestgaard BG 2010, unpublished results.
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EHR112F3: Lipoprotein cholesterol as a function of increasing levels of non-fasting triglycerides in the general population. Based on non-fasting samples from 36 160 men and women from the Copenhagen General Population Study collected over the period 2003–2007; 9% of men and 6% of women were on statins, mainly 40 mg/day simvastatin. Remnant cholesterol is calculated from a non-fasting lipid profile as total cholesterol minus HDL cholesterol minus LDL cholesterol; under these conditions, remnant cholesterol represents the total cholesterol transported in IDL, VLDL, and chylomicron remnants. Variable levels of chylomicrons are present in non-fasting samples and usually will only contribute minimally to the calculated remnant cholesterol. Nordestgaard BG 2010, unpublished results.

Mentions: First, it is important to ascertain the prevalence of atherogenic dyslipidaemia, i.e. the combination of elevated TRL remnants and/or low HDL-C.80 Among the general population plasma concentrations of total cholesterol, LDL-C and HDL-C are normally distributed. In contrast, the distributions of triglycerides, remnant cholesterol, apo B, and non-HDL-C (i.e. total cholesterol−HDL-C) tend to be skewed with a tail toward the highest levels. In the Copenhagen General Population Study, low HDL-C levels were frequently associated with elevated levels of cholesterol and TRL remnants (Figure 3). Approximately 45% of men and 30% of women in the study had triglycerides ≥1.7 mmol/L (150 mg/dL) with or without HDL-C < 1.0 mmol/L (40 mg/dL) (BG Nordestgaard, unpublished results). HDL-C levels are lower in Turkish populations, largely due to genetic predisposition.81,82 The Turkish Heart Study reported that ∼50% of men and ∼25% of women had HDL-C levels ≤0.9 mmol/L (35 mg/dL).82 As in other countries, atherogenic dyslipidaemia is on the rise, due to the increasing prevalence of the metabolic syndrome. In the Turkish Adults Risk Factor Study, ∼40% of men and 35% of women had triglycerides >1.7 mmol/L with or without low HDL-C (≤0.9 mmol/L or 35 mg/dL).83Figure 3


Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.

Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Nordestgaard BG, Ray KK, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A, Watts GF, European Atherosclerosis Society Consensus Pan - Eur. Heart J. (2011)

Lipoprotein cholesterol as a function of increasing levels of non-fasting triglycerides in the general population. Based on non-fasting samples from 36 160 men and women from the Copenhagen General Population Study collected over the period 2003–2007; 9% of men and 6% of women were on statins, mainly 40 mg/day simvastatin. Remnant cholesterol is calculated from a non-fasting lipid profile as total cholesterol minus HDL cholesterol minus LDL cholesterol; under these conditions, remnant cholesterol represents the total cholesterol transported in IDL, VLDL, and chylomicron remnants. Variable levels of chylomicrons are present in non-fasting samples and usually will only contribute minimally to the calculated remnant cholesterol. Nordestgaard BG 2010, unpublished results.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105250&req=5

EHR112F3: Lipoprotein cholesterol as a function of increasing levels of non-fasting triglycerides in the general population. Based on non-fasting samples from 36 160 men and women from the Copenhagen General Population Study collected over the period 2003–2007; 9% of men and 6% of women were on statins, mainly 40 mg/day simvastatin. Remnant cholesterol is calculated from a non-fasting lipid profile as total cholesterol minus HDL cholesterol minus LDL cholesterol; under these conditions, remnant cholesterol represents the total cholesterol transported in IDL, VLDL, and chylomicron remnants. Variable levels of chylomicrons are present in non-fasting samples and usually will only contribute minimally to the calculated remnant cholesterol. Nordestgaard BG 2010, unpublished results.
Mentions: First, it is important to ascertain the prevalence of atherogenic dyslipidaemia, i.e. the combination of elevated TRL remnants and/or low HDL-C.80 Among the general population plasma concentrations of total cholesterol, LDL-C and HDL-C are normally distributed. In contrast, the distributions of triglycerides, remnant cholesterol, apo B, and non-HDL-C (i.e. total cholesterol−HDL-C) tend to be skewed with a tail toward the highest levels. In the Copenhagen General Population Study, low HDL-C levels were frequently associated with elevated levels of cholesterol and TRL remnants (Figure 3). Approximately 45% of men and 30% of women in the study had triglycerides ≥1.7 mmol/L (150 mg/dL) with or without HDL-C < 1.0 mmol/L (40 mg/dL) (BG Nordestgaard, unpublished results). HDL-C levels are lower in Turkish populations, largely due to genetic predisposition.81,82 The Turkish Heart Study reported that ∼50% of men and ∼25% of women had HDL-C levels ≤0.9 mmol/L (35 mg/dL).82 As in other countries, atherogenic dyslipidaemia is on the rise, due to the increasing prevalence of the metabolic syndrome. In the Turkish Adults Risk Factor Study, ∼40% of men and 35% of women had triglycerides >1.7 mmol/L with or without low HDL-C (≤0.9 mmol/L or 35 mg/dL).83Figure 3

Bottom Line: If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered.Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates.These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

View Article: PubMed Central - PubMed

Affiliation: European Atherosclerosis Society, INSERM UMR-S939, Pitié-Salpetriere University Hospital, Paris 75651, France. john.chapman@upmc.fr

ABSTRACT
Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥ 1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.

Show MeSH
Related in: MedlinePlus