Landmark study
Residual cardiovascular risk similar in men and women
Focus on...
Non-fasting triglycerides: a predictor of ischaemic cardiovascular risk in Japanese subjects
The National Lipid Association (NLA)
The National Lipid Association (NLA) is a nonprofit, multidisciplinary medical society focused on enhancing the practice of lipid management in clinical medicine.
8 February 2015
Triglycerides: the tide has turned
Prof. Jean Charles Fruchart, Prof. Jean Davignon, Prof. Michel Hermans, Prof. Pierre Amarenco
Prof. Jean Charles Fruchart, Prof. Jean Davignon, Prof. Michel Hermans, Prof. Pierre Amarenco
An Editorial from the R3i Trustees

The Residual Risk Reduction Initiative (R3i) has long been an advocate of targeting atherogenic dyslipidaemia, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C), a driver of lipid-related residual cardiovascular risk in patients managed according to current standards of care, including statins. In the past, research had been focused on HDL-C, later shown to be a flawed presumption, implying that HDL-C is most likely a marker rather than a factor of cardiovascular risk...
R3i Education Channel
      MSDA 2014 - Experts interviews - Part 3 / 3

Pr Peter Libby

Pr Jean-Pierre Deprés

Pr Liping Zhao

What is inflammation relevant to the pathogenesis of insulin resistance?
Peter Libby
What is the mechanistic link between inflammation and the metabolic cluster?
Peter Libby
What are the criteria for overweight and obesity in Japan?
Jean-Pierre Després
What is the level of cardiovascular residual risk in Asian population?
Jean-Pierre Després
What is the value of BMI as a marker of risk?
Jean-Pierre Després
Gut microbiota is a complex ecological system how does it interact with our metabolism?
Liping Zhao
Novel apolipoprotein C-II mimetic peptide: future potential in targeting triglycerides?
This study reports data with a novel apoC-II mimetic peptide in an experimental mouse model (apolipoprotein E-knockout mice). This peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells, and activated lipolysis by lipoprotein lipase in vitro. Intravenous administration (30 mg/kg) to apolipoprotein E-knockout mice significantly reduced plasma cholesterol (by 38%) and triglycerides (by 85%), at 4 hours. The authors concluded that this novel peptide may offer future therapeutic potential for the management of elevated triglycerides.
A Novel apolipoprotein C-II mimetic peptide that activates lipoprotein lipase and decreases serum triglycerides in apolipoprotein E-knockout mice.
Amar MJ, Sakurai T, Sakurai-Ikuta A, Sviridov D, Freeman L, Ahsan L, Remaley AT.
Triglycerides in the news
Recent reviews highlight the case for triglycerides, more specifically triglyceride-rich lipoproteins (TRLs), in the development of cardiovascular risk.
Tenenbaum et al argue for re-consideration of the role of TRLs in cardiovascular disease, taking into account epidemiological, genetic and mechanistic data. This review also discusses mechanisms whereby TRLs stimulate atherogenesis, including excessive free fatty acid (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. As discussed by Khetarpal and Rader,2 genetic studies have provided convincing evidence that plasma levels of TRLs are causally related to the development of coronary artery disease (CAD), specifically implicating the key triglyceride-regulating enzyme lipoprotein lipase (LPL), in CAD risk. Beyond LPL, there is also strong evidence implicating the genes APOC3 and APOA5, encoding apolipoproteins (apo) C-III and apoA-V, respectively; data indicate that apoC-III promotes and apoA-V protects against CAD.
While the mainstay of management of hypertriglyceridaemia is lifestyle, genetic data also provide a rationale for the development of novel targeted therapies, such as an antisense APOC3 oligonucleotide, which offer the potential for reducing residual cardiovascular risk beyond that achieved with current therapy.
1. Khetarpal SA, Rader DJ. Triglyceride-rich lipoproteins and coronary artery disease risk. New insights from human genetics. Arterioscler Thromb Vasc Biol 2015 [Epub ahead of print].
2. Libby P. Triglycerides on the rise: should we swap seats on the seesaw? Eur Heart J 2014 [Epub ahead of print]
Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor
Tenenbaum A, Klempfner R, Fisman EZ. Hypertriglyceridemia
CETP gene-diet interaction impacts atherogenic dyslipidaemia
A new report provides evidence of an interaction between cholesteryl ester transfer protein (CETP) genotype and diet on changes in blood lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides, i.e. atherogenic dyslipidaemia).
This study evaluated whether the common CETP rs3764261 genotype influenced lipid changes in response to weight-loss diets, specifically the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) and Dietary Intervention Randomized Controlled Trial (DIRECT) studies. In the POUNDS LOST study in 732 overweight/obese adults, those carrying the CETP-rs3764261 CC genotype and on a high-fat diet had larger increases in HDL-C (10.1% vs 4.5%, p=0.001) and decreases in triglycerides (24.0% vs 14.7%, p=0.007) than individuals on a low-fat diet at 6 months. These gene-diet interactions affecting changes in HDL-C and triglycerides were replicated in the DIRECT study. The authors concluded that individuals with the CETP rs3764261 CC genotype might derive greater benefit in targeting atherogenic dyslipidaemia with a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet.
CETP genotype and changes in lipid levels in response to weight-loss diet intervention: gene-diet interaction analysis in the POUNDS LOST and DIRECT randomized trials.
Qi Q, Durst R, Schwarzfuchs D, Leitersdorf E, Shpitzen S, Li Y, Wu H, Champagne CM, Hu FB, Stampfer MJ, Bray GA, Sacks FM, Shai I, Qi L.
Does microvascular disease predict macrovascular disease?
A previous review by the Residual Risk Reduction Initiative highlighted a link between microvascular and macrovascular disease in type 2 diabetes.(1) This new study adds to the evidence, suggesting that retinal microvascular endothelial dysfunction is a marker for underlying coronary artery disease (CAD) in non-diabetic subjects.
The study investigated 197 subjects, 119 without CAD but at least 2 cardiovascular risk factors (non-CAD controls) and 78 with stable CAD, using retinal arteriolar and venular dilatation to flicker light, a nitric oxide dependent phenomenon, as a marker of retinal microvascular endothelial dysfunction. Fingertip pulse volume amplitude to calculate reactive hyperaemia index (RHI) and brachial artery flow-mediated dilatation (FMD) were measures of peripheral microvascular and conduit vessel endothelial function, respectively. There was attenuation of mean retinal arteriolar dilatation in subjects with CAD (1.51±1.51% vs 2.37±1.95% in non-CAD controls; p = 0.001). Even after adjustment for age, gender, cardiovascular risk factors and medication use, retinal arteriolar dilatation remained independently associated with CAD (odds ratio 1.60, 95% CI 1.14, 2.25; p = 0.007). In conclusion, this study provides further support of a link between microvascular and macrovascular disease.
1. Rosenson RS, Fioretto P, Dodson PM. Does microvascular disease predict macrovascular events in type 2 diabetes? Atherosclerosis 2011;218:13-8.
Usefulness of retinal microvascular endothelial dysfunction as a predictor of coronary artery disease.
Al-Fiadh AH, Wong TY, Kawasaki R, Clark DJ, Patel SK, Freeman M, Wilson A, Burrell LM, Farouque O.
US Diabetes and obesity costs updated
Recent data from the U.S. show reduced life expectancy and increased lifetime healthcare expenditure in obese individuals with diabetes compared with those of normal weight. These data highlight the urgent need to tackle the escalating burden of cardiometabolic disease in the US and beyond. The analysis included data from the National Health Interview Survey (NHIS, 1997-2000), the Medical Expenditure Panel Survey (1997-2000), and the NHIS Linked Mortality Public-use Files, with mortality followed-up to 2006. Markov modelling with risk and cost estimates was used to compute life years and total lifetime healthcare expenditures by age, race, sex, and body mass index (BMI) classifications for patients with or without diabetes. The presence of diabetes not only decreased life expectancy by 3.3 to 18.7 years, but also increased lifetime healthcare expenditures by $8,946 to $159,380, depending on age-race-sex-BMI classification groups. In U.S. adults aged 50 years, white females with diabetes and BMI >40 kg/m2 had 17.9 remaining life years and lifetime health expenditures of $185,609. By comparison, females with diabetes and normal weight had 22.2 remaining life years and lifetime health expenditures of $183,704. These data reinforce evidence on the costs of obesity, in terms of decreased life expectancy and increased lifetime healthcare expenditure.
Life years lost and lifetime healthcare expenditures associated with diabetes in the U.S., National Health Interview Survey, 1997–2000.
Leung MM, Pollack LM, Colditz GA, Chang SH.
Impact of diabetic retinopathy in working age individuals
The cost and impact on daily life of diabetic retinopathy (DR) and diabetic macular oedema (DME) were highlighted by this US retrospective cohort study, using claims data (2001-2012) from the Human Capital Management Services Group Research Reference Database on annual direct/indirect health benefit costs and absences for employees aged ? 18 years, total data (n=466,251). Employees were divided into two groups, drivers (n=39,702) or nondrivers (n=426,549). Among nondrivers with diabetes, the presence of DME or DR significantly increased sick leave and short-term disability costs. Thus, this study using real-world data highlights the need for renewed emphasis on early detection and management of diabetes-related eye disease in working-age adults. Beyond mandatory management of blood glucose and blood pressure, data from two major prospective studies support a role for fenofibrate in the management of early DR. As recommended by the R3i, incorporation of fenofibrate into management algorithms may help to reduce costs and improve quality of life among patients with diabetes.(1)
1. Hermans MP, Fruchart JC, Davignon J et al. Residual microvascular risk in type 2 diabetes in 2014: Is it time for a re-think? A perspective from the Residual Risk Reduction Initiative (R3i). Journal of Diabetes & Metabolism 2014, 5:413.
United States comparative costs and absenteism of diabetic ophthalmic conditions.
Brook RA, Kleinman NL, Patel S, Smeeding JE, Beren IA, Turpcu A.