Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease

Hoogeveen, Ron C.; Gaubatz, John W.; Sun, Wei; Dodge, Rhiannon; Crosby, Jacy R.; Jiang, Jennifer; Couper, David J.; Virani, Salim S.; Kathiresan, Sekar; Boerwinkle, Eric; Ballantyne, Christie M.

doi:10.1161/atvbaha.114.303284

Cited by 416 publications

(366 citation statements)

References 47 publications

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“…It is also a strength that we show similar results for HDL cholesterol, HDL3 cholesterol, HDL2 cholesterol, and apolipoprotein A1, all of which are strongly inversely correlated with increased concentrations of remnant cholesterol, but by themselves are unlikely to be causally related to cardiovascular disease (10,32 ). Finally, it is reassuring that apolipoprotein B, which marks LDL and remnant cholesterol combined, has risk estimated to be in between those for LDL and remnant cholesterol; however, it is slightly surprising that small dense LDL cholesterol was not associated with all-cause mortality, as small dense LDL cholesterol (like HDL cholesterol) is inversely correlated with triglycerides and remnant cholesterol and has previously been associated with cardiovascular disease events with the same assay as used here (33 ).…”

Section: Discussionmentioning

confidence: 62%

Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease

et al. 2016

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BACKGROUND Increased concentrations of remnant cholesterol are causally associated with increased risk of ischemic heart disease. We tested the hypothesis that increased remnant cholesterol is a risk factor for all-cause mortality in patients with ischemic heart disease. METHODS We included 5414 Danish patients diagnosed with ischemic heart disease. Patients on statins were not excluded. Calculated remnant cholesterol was nonfasting total cholesterol minus LDL and HDL cholesterol. During 35836 person-years of follow-up, 1319 patients died. RESULTS We examined both calculated and directly measured remnant cholesterol; importantly, however, measured remnant cholesterol made up only 9% of calculated remnant cholesterol at nonfasting triglyceride concentrations <1 mmol/L (89 mg/dL) and only 43% at triglycerides >5 mmol/L (443 mg/dL). Multivariable-adjusted hazard ratios for all-cause mortality compared with patients with calculated remnant cholesterol concentrations in the 0 to 60th percentiles were 1.2 (95% CI, 1.1–1.4) for patients in the 61st to 80th percentiles, 1.3 (1.1–1.5) for the 81st to 90th percentiles, 1.5 (1.1–1.8) for the 91st to 95th percentiles, and 1.6 (1.2–2.0) for patients in the 96th to 100th percentiles (trend, P < 0.001). Corresponding values for measured remnant cholesterol were 1.0 (0.8–1.1), 1.2 (1.0–1.4), 1.1 (0.9–1.5), and 1.3 (1.1–1.7) (trend, P = 0.006), and for measured LDL cholesterol 1.0 (0.9–1.1), 1.0 (0.8–1.2), 1.0 (0.8–1.3), and 1.1 (0.8–1.4) (trend, P = 0.88). Cumulative survival was reduced in patients with calculated remnant cholesterol ≥1 mmol/L (39 mg/dL) vs <1 mmol/L [log-rank, P = 9 × 10−6; hazard ratio 1.3 (1.2–1.5)], but not in patients with measured LDL cholesterol ≥3 mmol/L (116 mg/dL) vs <3 mmol/L [P = 0.76; hazard ratio 1.0 (0.9–1.1)]. CONCLUSIONS Increased concentrations of both calculated and measured remnant cholesterol were associated with increased all-cause mortality in patients with ischemic heart disease, which was not the case for increased concentrations of measured LDL cholesterol. This suggests that increased concentrations of remnant cholesterol explain part of the residual risk of all-cause mortality in patients with ischemic heart disease.

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Section: Discussionmentioning

confidence: 62%

Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease

et al. 2016

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“…Each major lipoprotein class in the standard lipid profi le (VLDL, LDL, and HDL) consists of subclasses that are heterogeneous in size, density, and potentially in atherogenicity ( 15,16 ). Circulating levels of these subclasses can predict CVD events (17)(18)(19).…”

Section: Nmr-lspmentioning

confidence: 99%

Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in type 1 diabetes

Zhang

Jenkins

Basu

et al. 2016

Journal of Lipid Research

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The Diabetes Control and Complications Trial (DCCT) was a randomized trial comparing the effects of intensive (multiple daily insulin injections or insulin pump therapy aimed at near-normalization of blood glucose levels) versus conventional therapy (usually twice daily insulin injections) on the development and progression of micro-vascular complications of type 1 diabetes ( 1 ). The trial achieved and sustained a reduction of two percentage points in HbA 1c in the intensive versus conventional therapy groups, and demonstrated conclusively that intensive therapy delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy ( 1 ). During the observational follow-up study of DCCT [known as the Epidemiology of Diabetes Intervention and Complications (EDIC) study ( 2 )], prior intensive therapy was associated with long-term reductions in Abstract Our objective is to defi ne differences in circulating lipoprotein subclasses between intensive versus conventional management of type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). NMR-determined lipoprotein subclass profi les (NMR-LSPs), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of 5 years (interquartile range: 4-6 years) of randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSPs between treatment groups. Standard total, LDL, and HDL cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSPs showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, P = 0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, P = 0.007), total IDL/LDL (mean: 1,000 vs. 1,053 nmol/l, P = 0.01), and small HDL (mean: 17.3 vs. 18.6 mol/l, P < 0.0001), the latter accounting for reduced total HDL (mean: 33.8 vs. 34.8 mol/l, P = 0.01). In conclusion, intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the benefi cial effects of intensive diabetes management on vascular

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“…Increased proportions of small and dense LDL have been consistently associated with cardiovascular risk (64), and some special groups of individual, such as DM (65) or metabolic syndrome (66) carriers, show this phenotype more frequently. Several researchers consider that more specific dosage of LDL particles is a promising technique to refine the prediction of cardiovascular risk (64,67).…”

Section: Cetp and Its Lipoprotein Subclassesmentioning

confidence: 99%

“…Several researchers consider that more specific dosage of LDL particles is a promising technique to refine the prediction of cardiovascular risk (64,67). However, this measurement still needs to become easier to be more widely used in clinical practice.…”

Section: Cetp and Its Lipoprotein Subclassesmentioning

confidence: 99%

Reassessing lipid metabolism and its potentialities in the prediction of cardiovascular risk

Silva

Almeida-Pititto

Ferreira

2015

Arch. Endocrinol. Metab.

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There are numerous particles, enzymes, and mechanisms in the lipid metabolism that are involved in the genesis of cardiovascular disease (CVD). Given its prevalence in populations and its impact on mortality, it is relevant to review the lipid metabolism as it may potentially provide subsidies to better prediction. This article reviews the importance of traditional cardiovascular risk factors and comments on the potential of novel lipid biomarkers involved in the physiopathology of CVD. The Framingham cohorts proved the role of traditional risk factors (physical inactivity, smoking, blood pressure, total cholesterol, LDL-C, HDL-C, plasma glucose) in the prediction of cardiovascular events. However, a significant number of individuals that suffer from a cardiovascular event has few or none of these factors. Such finding indicates the need for new biomarkers able to identify plaques that are more susceptible to rupture. Some of bloodstream biomarkers related to lipid metabolism are modified LDL particles, apolipoprotein AI (apo AI), apolipoprotein B, lipoprotein (a) [Lp (a)], cholesteryl ester transfer protein (CETP), subtypes of LDL and HDL particles, and lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). These factors participate in the atherosclerotic process, and are abnormal in individuals at high risk, or in those who suffered from a cardiovascular event. Lp (a) determination is already employed in clinical practice and should be included as a reference parameter for CVD monitoring. Furthermore, there are expectations for wider use of apo B, non-HDL cholesterol and total cholesterol / HDL-C determination to improve cardiovascular risk assessment. Arch Endocrinol Metab. 2015;59(2):171-80

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Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease

Cited by 416 publications

References 47 publications

Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease

Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease

Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in type 1 diabetes

Reassessing lipid metabolism and its potentialities in the prediction of cardiovascular risk

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