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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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Related in: MedlinePlus

Relationship of non-fasting triglycerides (up to and >5 mmol/L or 440 mg/dL) and risk of myocardial infarction, ischaemic stroke, and total mortality. Results are shown as age-adjusted hazard ratios from the Copenhagen City Heart Study with 26–31 years of follow-up. Reproduced with modification from Nordestgaard et al.89 and Freiberg et al.90 Copyright© (2007, 2008) American Medical Association. All rights reserved.
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EHR112F5: Relationship of non-fasting triglycerides (up to and >5 mmol/L or 440 mg/dL) and risk of myocardial infarction, ischaemic stroke, and total mortality. Results are shown as age-adjusted hazard ratios from the Copenhagen City Heart Study with 26–31 years of follow-up. Reproduced with modification from Nordestgaard et al.89 and Freiberg et al.90 Copyright© (2007, 2008) American Medical Association. All rights reserved.

Mentions: While coronary risk was increased by 37% (95% CI 31–42%) per SD increase in loge triglycerides, this association was weakened after adjustment for HDL-C and abrogated after correction for non-HDL-C. Additionally, triglycerides were not associated with stroke risk after adjustment for other lipid factors.93 These data are compatible with the view that it is the number of TRL and remnant particles that cause CVD. Thus, the risk associated with elevated triglycerides can be explained by this lipid acting as a marker for increased numbers of TRL, which in turn are closely associated with the combination of higher levels of non-HDL-C and low levels of HDL-C. In the Copenhagen City Heart Study, increased risk for MI, ischaemic stroke, and mortality was evident at markedly elevated triglycerides (>5.0 mmol/L or >450 mg/dL), although these data were not adjusted for non-HDL-C (Figure 5).89,90 Thus, low HDL-C and elevated non-HDL-C and triglycerides appear to be relevant to CV risk beyond LDL-C.Figure 5


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)

Relationship of non-fasting triglycerides (up to and >5 mmol/L or 440 mg/dL) and risk of myocardial infarction, ischaemic stroke, and total mortality. Results are shown as age-adjusted hazard ratios from the Copenhagen City Heart Study with 26–31 years of follow-up. Reproduced with modification from Nordestgaard et al.89 and Freiberg et al.90 Copyright© (2007, 2008) American Medical Association. All rights reserved.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHR112F5: Relationship of non-fasting triglycerides (up to and >5 mmol/L or 440 mg/dL) and risk of myocardial infarction, ischaemic stroke, and total mortality. Results are shown as age-adjusted hazard ratios from the Copenhagen City Heart Study with 26–31 years of follow-up. Reproduced with modification from Nordestgaard et al.89 and Freiberg et al.90 Copyright© (2007, 2008) American Medical Association. All rights reserved.
Mentions: While coronary risk was increased by 37% (95% CI 31–42%) per SD increase in loge triglycerides, this association was weakened after adjustment for HDL-C and abrogated after correction for non-HDL-C. Additionally, triglycerides were not associated with stroke risk after adjustment for other lipid factors.93 These data are compatible with the view that it is the number of TRL and remnant particles that cause CVD. Thus, the risk associated with elevated triglycerides can be explained by this lipid acting as a marker for increased numbers of TRL, which in turn are closely associated with the combination of higher levels of non-HDL-C and low levels of HDL-C. In the Copenhagen City Heart Study, increased risk for MI, ischaemic stroke, and mortality was evident at markedly elevated triglycerides (>5.0 mmol/L or >450 mg/dL), although these data were not adjusted for non-HDL-C (Figure 5).89,90 Thus, low HDL-C and elevated non-HDL-C and triglycerides appear to be relevant to CV risk beyond LDL-C.Figure 5

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