Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study

McNamara, Judith; Shah, Paulesh K.; Nakajima, Katsuyuki; Cupples, L. Adrienne; Wilson, Peter W.F.; Ordovas, José M.; Schaefer, Ernst J.

doi:10.1016/s0021-9150(00)00484-6

Cited by 260 publications

(156 citation statements)

References 56 publications

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“…Notably, there are strikingly different RLP‐C levels across studies 10, 27, 28, 43. These differences strongly suggest that the methods used (ie, immunoseparation, ultracentrifugation) have significantly different profiles or sensitivities for separating and measuring remnant lipoproteins.…”

Section: Discussionmentioning

confidence: 97%

“…In a cross‐sectional analysis from >1500 women in the Framingham Heart Study, RLP‐C levels were independently associated with prevalent cardiovascular disease 10. Careful attention should be paid to sex‐based differences in future analyses of remnants‐related risk.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple prospective cohorts from around the world consistently suggest a link between RLPs, often reflected by serum TG measurements, and CHD 8, 9, 10, 11. Historically, some studies have suggested that this association is attenuated by the inclusion of other potentially causal factors such as HDL‐C, thus raising the question of whether RLPs may represent a surrogate for other causative factors in atherosclerotic disease 12, 13.…”

Section: Introductionmentioning

confidence: 99%

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Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

Joshi

Khokhar

Massaro

et al. 2016

JAHA

143

102

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BackgroundRemnant lipoproteins (RLPs), the triglyceride‐enriched precursors to low‐density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP‐C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.Methods and ResultsWe analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable‐adjusted hazard ratios (HRs) for RLP‐C (the sum of very low‐density lipoprotein3 cholesterol and intermediate‐density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid‐lowering therapy for the combined population, RLP‐C (HR 1.23 per 1‐SD increase, 95% CI 1.06–1.42, P<0.01) and intermediate‐density lipoprotein cholesterol (HR 1.26 per 1‐SD increase, 95% CI 1.08–1.47, P<0.01) predicted CHD during an 8‐year follow‐up. Associations were attenuated by high‐density lipoprotein cholesterol and ultimately lost significance with inclusion of real low‐density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.Conclusion RLP‐C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP‐C to prevent CHD warrant further intensive investigation.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

Joshi

Khokhar

Massaro

et al. 2016

JAHA

143

102

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“…Postprandial triglyceride-rich lipoproteins and especially chylomicron remnants have been implicated as risk factors for atherosclerosis and progression of coronary artery disease [41][42][43][44][45]. Although the physiological basis of metabolic dyslipidaemia appears to be hepatic overproduction of apo-B-containing VLDL particles [46,47], emerging evidence suggests that intestinal overproduction of apo-B-48-containing lipoproteins in insulin-resistant states may be an important contributor to the elevation of circulating triglyceride-rich lipoproteins [17,18,48].…”

Section: Discussionmentioning

confidence: 99%

Overproduction of intestinal lipoprotein containing apolipoprotein B-48 in Psammomys obesus: impact of dietary n-3 fatty acids

et al. 2006

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Aims/hypothesis Emerging evidence underscores the important role of the small intestine in the pathogenesis of dyslipidaemia in insulin resistance and type 2 diabetes. We therefore tested the hypothesis that n-3 fatty acids improve the various events governing intra-enterocyte lipid transport in Psammomys obesus gerbils, a model of nutritionally induced metabolic syndrome. Materials and methods Experiments were carried out on Psammomys obesus gerbils that were assigned to an isocaloric control diet and a diet rich in fish oil for 6 weeks. Results Increased dietary intake of fish oil lowered body weight and improved hyperglycaemia and hyperinsulinaemia. It simultaneously decreased de novo intestinal lipogenesis and lipid esterification of the major lipid classes, e.g. triglycerides, phospholipids and cholesteryl esters, particularly in insulinresistant and diabetic animals. Accordingly, lessened activity of monoacylglycerol and diacylglycerol acyltransferase was recorded. As assessed in cultured jejunal explants incubated with either [ 14 C]-oleic acid or [ 35 S]-methionine, fish oil feeding resulted in diminished triglyceride-rich lipoprotein assembly and apolipoprotein (apo) B-48 biogenesis, respectively. The mechanisms did not involve apo B-48 transcription or alter the gene expression and activity of the critical microsomal triglyceride transfer protein. Rather, the suppressed production of apo B-48 by n-3 fatty acids was associated with intracellular proteasome-mediated posttranslational downregulation in insulin-resistant and diabetic animals. Conclusions/interpretation Our data highlight the beneficial impact of n-3 fatty acids on adverse effects of the metabolic syndrome and emphasise their influence on intestinal lipid transport, an effect which may limit postprandial lipaemia and the risk of atherosclerosis.

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“…These remnants are highly associated with CVD, especially in women [57]. Given their small size, they can cross the endothelium, and in the subendothelium are considered modified lipoproteins and are phagocytosed by macrophages [58].…”

Section: Dyslipidemiamentioning

confidence: 99%

Abdominal Obesity and Metabolic Alterations in the Menopausal Transition

Berg

Mesch

Siseles

2012

Curr Obstet Gynecol Rep

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The prevalence of overweight and obesity is strikingly increasing worldwide. Obesity is a major risk factor for non-insulin-dependent diabetes mellitus, cardiovascular diseases, and cancer, and is also associated with various psychosocial consequences. Menopausal transition is associated with unfavorable changes in body composition and abdominal fat deposition, which is accompanied by an increment of insulin resistance/hyperinsulinemia, a decrease in sex hormone-binding globulin levels and, consequently, an increase in free testosterone and greater androgenicity. Central body fat also correlates with deleterious changes in adipokines and inflammation markers like leptin, C-reactive protein, and adiponectin. In addition, the greater deposition of visceral fat in the menopausal transition contributes to the development of an atherogenic lipoprotein profile, which includes high triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations, as well as an increment of small dense low-density lipoprotein (LDL) subfraction, intermediate density lipoproteins (IDL), apolipoprotein (apo) B/apo A-I ratio and lipoprotein(a).

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Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study

Cited by 260 publications

References 56 publications

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies

Overproduction of intestinal lipoprotein containing apolipoprotein B-48 in Psammomys obesus: impact of dietary n-3 fatty acids

Abdominal Obesity and Metabolic Alterations in the Menopausal Transition

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