Triglycerides and Cardiovascular Disease

Miller, Michael; Stone, Neil J.; Ballantyne, Christie M.; Bittner, Vera; Criqui, Michael H.; Ginsberg, Henry N.; Goldberg, Anne C.; Howard, W.J.; Jacobson, Mark Z.; Kris-Etherton, Penny M.; Lennie, Terry A.; Levi, Moshe; Mazzone, Theodore; Pennathur, Subramanian

doi:10.1161/cir.0b013e3182160726

Cited by 1,591 publications

(1,012 citation statements)

References 569 publications

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“…The overweight dogs had the highest peak triglyceride concentration, but their values were approximately half of that reported in an earlier study of obese dogs 11. The results give some support to the existence of a close relationship between triglyceride concentrations and body fat, which is reported both in people28 and dogs 29…”

Section: Discussionsupporting

confidence: 76%

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

Söder

Wernersson

Hagman

et al. 2016

Veterinary Internal Medicne

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BackgroundObese dogs risk poor life quality, creating a need for increased knowledge of metabolism in overweight dogs.ObjectivesInvestigate postprandial metabolic and hormonal responses to a high‐fat mixed‐meal in dogs and responses of lean versus overweight dogs.AnimalsTwenty‐eight healthy intact male Labrador Retrievers were included.MethodsProspective observational study. Twelve dogs were grouped as lean (body condition score (BCS 4–5), 10 as slightly overweight (BCS 6), and 6 as overweight (BCS 6.5–8) on a 9‐point scale. After an overnight fast, urine and blood samples were collected. Dogs were then fed a high‐fat mixed‐meal, and blood was collected hourly for 4 hours and urine after 3 hours.ResultsPostprandial concentrations of insulin and glucagon were increased at 1 hour (both P < 0.0001), triglycerides at 2 hours (P < 0.0001), and glucose at 3 hours (P = 0.004); and all remained increased throughout the feed‐challenge in all dogs. Postprandial urine cortisol/creatinine ratio was higher than fasting values (P = 0.001). Comparing between groups, there was an overall higher triglyceride response in overweight compared to lean (P = 0.001) and slightly overweight (P = 0.015) dogs. Overweight dogs also had higher fasting cortisol/creatinine ratio compared to lean dogs (P = 0.024).Conclusions and Clinical ImportancePostprandial responses of dogs to a high‐fat mixed‐meal were similar to those previously reported in people. The higher postprandial triglyceride response and fasting cortisol/creatinine ratio in the overweight dogs could be early signs of metabolic imbalance. Thus, although overweight dogs often appear healthy, metabolic alterations might be present.

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Section: Discussionsupporting

confidence: 76%

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

Söder

Wernersson

Hagman

et al. 2016

Veterinary Internal Medicne

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“…Experimental evidence suggests that VLDLs and their contents could contribute to the pathogenesis of ASCVD, potentially through increased expression of proinflammatory cytokines, adhesion molecules, and coagulation factors, as well as enhanced recruitment and attachment of monocytes to endothelium, induction of endothelial cell apoptosis, and impairment of the anti‐inflammatory properties of HDL 5, 10, 12, 13, 14, 15, 16. Differences in VLDL size and composition may determine their predilection for uptake into the neointima of atheroma 27.…”

Section: Discussionmentioning

confidence: 99%

“…Such residual risk may reflect aspects of atherogenesis not captured by LDL‐C, including effects of very‐low‐density lipoproteins (VLDLs) and their contents (cholesterol and triglycerides) 5, 6, 7, 8, 9. Enzymatic hydrolysis of VLDL results in the formation of smaller, cholesterol‐enriched lipoprotein particles,5, 10, 11 which experimental studies suggest could contribute to the development of ASCVD 5, 7, 10, 12, 13, 14, 15, 16. Clinically, however, there has been uncertainty as to whether ASCVD events could be further reduced by reducing these triglyceride‐rich lipoproteins, with several neutral trials examining this strategy to date 10, 17…”

mentioning

confidence: 99%

Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions in Very‐Low‐Density Lipoproteins

Lawler

Akinkuolie

Harada

et al. 2017

JAHA

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BackgroundIt is uncertain whether pharmacological reductions in very‐low‐density lipoproteins (VLDLs), and their component triglyceride and cholesterol could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD) events among individuals in whom low‐density lipoprotein cholesterol (LDL‐C) has been adequately lowered. We examined whether individuals with greater on‐statin reductions in VLDL‐related measures—beyond reductions in LDL‐C—were at further reduced risk of ASCVD.Methods and ResultsIn 9423 participants in the JUPITER (Justification for the Use of Statins in Prevention) trial (NCT00239681), at baseline and on statin we measured standard lipids, 400‐MHz proton nuclear magnetic resonance spectroscopy‐measured VLDL particle subclasses (small, medium, and large VLDL lipoprotein particle concentration), and total VLDL cholesterol mass. Compared with individuals allocated to placebo, we examined risk of incident ASCVD (N=211) among statin‐allocated participants who achieved minimal (

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“…Despite remarkable capacity to lower low‐density lipoprotein cholesterol (LDL‐C) with the use of statins and other drugs, coronary heart disease (CHD) persists as a leading cause of morbidity and mortality in the United States 1, 2. Apolipoprotein B (apoB) and non–high‐density lipoprotein cholesterol (non–HDL‐C) levels are superior predictors of CHD risk compared with LDL‐C 3.…”

Section: Introductionmentioning

confidence: 99%

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

Joshi

Khokhar

Massaro

et al. 2016

JAHA

141

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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Triglycerides and Cardiovascular Disease

Cited by 1,591 publications

References 569 publications

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions in Very‐Low‐Density Lipoproteins

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

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