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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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Hazard ratios for coronary heart disease and ischaemic stroke across quantiles of usual concentrations of triglycerides, HDL, and non-HDL cholesterol levels. Reproduced with permission from the Emerging Risk Factors Collaboration.93 Copyright© (2009) American Medical Association. All rights reserved.
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EHR112F4: Hazard ratios for coronary heart disease and ischaemic stroke across quantiles of usual concentrations of triglycerides, HDL, and non-HDL cholesterol levels. Reproduced with permission from the Emerging Risk Factors Collaboration.93 Copyright© (2009) American Medical Association. All rights reserved.

Mentions: The Emerging Risk Factors Collaboration (ERFC)93 provides the most robust evidence for the association of HDL-C with CV risk (Figure 4). This analysis of 68 studies in 302 430 participants without prior history of CVD used individual participant data, allowing for harmonization and consistent adjustment of confounding factors, hitherto unfeasible. HDL-C was strongly associated with coronary risk even after adjustment for non-HDL-C and loge triglycerides and non-lipid risk factors. Each unit of standard deviation (SD) increase in HDL-C concentration (0.38 mmol/L or 15 mg/dL) was associated with 22% reduction in CHD risk. Importantly, this protective effect was equal across the range of triglyceride levels. However, it is acknowledged that the data are not clear for HDL-C levels <0.5 or >2.2–2.5 mmol/L (<19 mg/dL or >85–100 mg/dL). Non-HDL-C and apo B each had very similar associations with CHD. Both HDL-C and non-HDL-C were also modestly associated with ischaemic stroke (Figure 4), but not haemorrhagic stroke.Figure 4


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)

Hazard ratios for coronary heart disease and ischaemic stroke across quantiles of usual concentrations of triglycerides, HDL, and non-HDL cholesterol levels. Reproduced with permission from the Emerging Risk Factors Collaboration.93 Copyright© (2009) American Medical Association. All rights reserved.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHR112F4: Hazard ratios for coronary heart disease and ischaemic stroke across quantiles of usual concentrations of triglycerides, HDL, and non-HDL cholesterol levels. Reproduced with permission from the Emerging Risk Factors Collaboration.93 Copyright© (2009) American Medical Association. All rights reserved.
Mentions: The Emerging Risk Factors Collaboration (ERFC)93 provides the most robust evidence for the association of HDL-C with CV risk (Figure 4). This analysis of 68 studies in 302 430 participants without prior history of CVD used individual participant data, allowing for harmonization and consistent adjustment of confounding factors, hitherto unfeasible. HDL-C was strongly associated with coronary risk even after adjustment for non-HDL-C and loge triglycerides and non-lipid risk factors. Each unit of standard deviation (SD) increase in HDL-C concentration (0.38 mmol/L or 15 mg/dL) was associated with 22% reduction in CHD risk. Importantly, this protective effect was equal across the range of triglyceride levels. However, it is acknowledged that the data are not clear for HDL-C levels <0.5 or >2.2–2.5 mmol/L (<19 mg/dL or >85–100 mg/dL). Non-HDL-C and apo B each had very similar associations with CHD. Both HDL-C and non-HDL-C were also modestly associated with ischaemic stroke (Figure 4), but not haemorrhagic stroke.Figure 4

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