Landmark study
Atherogenic dyslipidaemia: underdiagnosed and undertreated
Focus on...
Visceral adipose tissue predicts development of atherogenic dyslipidaemia
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.
MSDA 2015 Congress
11 January 2016

Looking back at 2015: lipid highlights

Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco
Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco
An Editorial from the R3i Trustees

The last 12 months has been an exciting time for lipid research, led by the advance of proprotein convertase subtilisin/kexin type 9 (PCSK9) targeted therapy. Indeed, the American Heart Association (AHA) has cited the PCSK9 inhibitors alirocumab and evolocumab as two of the top 10 research advances of 2015.
Preliminary data in March suggested that PCSK9 monoclonal antibody therapy, on top of statin, reduced major cardiovascular events by about 50% in high cardiovascular risk patients. Despite the lack of definitive outcomes data, the first two agents in this class were licensed in Europe and the USA earlier this year. With the first of the outcomes studies with these agents (evolocumab) due to report in late 2016, we will finally be able to evaluate whether these novel agents can reduce lipid-related residual cardiovascular risk that persists despite statin therapy.
R3i Education Channel

SPEAD-A: Alogliptin slows progression of atherosclerosis in type 2 diabetes

Alogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that decreases plasma glucose and has also been shown to improve postprandial triglycerides and triglyceride-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. While in the EXAMINE study (1), cardiovascular event rates were not higher with alogliptin than with placebo in type 2 diabetes patients with recent acute coronary syndrome, experimental studies suggested a beneficial effect on atherosclerosis progression in animal models. These findings provided a rationale for further clinical investigation in SPEAD-A (Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis). SPEAD-A was a prospective, randomized, open-label, blinded-end point study in 341 (mean age 64.4 years, 83% male) patients with type 2 diabetes but without history of cardiovascular disease. Patients were randomly allocated to treatment with alogliptin (n=172) or conventional management (n=169). The primary outcomes were changes in mean common and maximum intima-media thickness (IMT) of the carotid artery, measured by carotid arterial echography, over 24 months. Compared with conventional management, alogliptin was associated with significant attenuation of atherosclerosis progression, as assessed by improvement in mean common IMT (?0.026 mm [standard error, SE 0.009] vs. 0.005 mm [SE 0.009] with conventional management, p = 0.022) and maximum IMT of the right and left carotid arteries ( ?0.045 mm [SE 0.018] vs. 0.011 mm [SE 0.017], p = 0.025, and ?0.079 mm [SE 0.018] vs. ?0.015 mm [SE 0.018], p= 0.013, respectively). Based on these findings, the authors propose a large-scale prospective trial to evaluate the utility of DPP-4 inhibitors for primary prevention of cardiovascular disease in type 2 diabetes.
1. White WB, Cannon CP, Heller SR et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369:1327-1335
Alogliptin, a Dipeptidyl Peptidase-4 Inhibitor, prevents the progression of carotid atherosclerosis in patients with type 2 diabetes: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)
Mita T, Katakami N, Yoshii H et al.

Genetic variants of peroxisome proliferator-activated receptor ? linked with susceptibility to diabetic retinopathy

Diabetic retinopathy, one of the key reasons for loss of vision, is associated with substantial morbidity, disability and cost. Yet despite extensive research, the exact mechanism(s) responsible have yet to be fully elucidated. A pathogenic role of diabetes-induced peroxisome proliferator-activated receptor alpha (PPAR-alpha) down-regulation in microvascular dysfunction was previously reported (1). This study implicates PPAR-alpha with diabetic retinopathy in a cohort of Chinese type 2 diabetes patients. The study included 812 type 2 diabetes patients (373 men, 439 women, mean age 53.3±14.0 years), of whom 402 had diabetic retinopathy. The authors looked at the association between three single nucleotide polymorphisms previously shown to be associated with PPAR-alpha: rs4253778, rs135539 and rs1800206. Homozygous carriers of the variant rs1800206 had a 22% decreased risk of diabetic retinopathy compared with those with wild-type homozygotes (odds ratio 0.78, 95% confidence interval [CI] 0.66-0.94). There was also evidence of a potential genetic interaction between rs1800206 and the Leu162 allele, associated with the presence of abdominal obesity. Carriers with abdominal obesity had the lowest risk of diabetic retinopathy (odds ratio 0.39, 95% CI 0.30-0.74), after adjustment. In conclusion, this study indicates potential interaction between genetic determinants of PPAR-alpha, abdominal obesity and diabetic retinopathy in this population cohort.
1. Hu Y, Chen Y, Ding L et al. Pathogenic role of diabetes-induced PPAR-alpha down-regulation in microvascular dysfunction. Proc Natl Acad Sci U S A. 2013;110:15401-6.
The association of peroxisome proliferator-activated receptor alpha with diabetic retinopathy, and additional gene-obesity interaction in Chinese type 2 diabetes mellitus patients.
Qi S, Wang C, Zhang Y et al

Remnant cholesterol linked with premature MI

Previous reports have identified that remnant cholesterol, the cholesterol present in triglyceride-rich lipoproteins, is associated with elevated cardiovascular disease risk. This study adds new evidence showing that remnant cholesterol is a risk marker in young individuals with acute myocardial infarction (AMI). This prospective, multicentre, case-control study included 102 consecutive AMI survivors (?40 years) and 200 controls, matched for age, gender and centre. Overall, individuals with AMI had remnant cholesterol levels that were 1.7-fold higher compared with controls (61.1 ± 36.8 vs 35.8 ± 16.8 mg/dL, p <0.001). Each 1 standard deviation increase in remnant cholesterol was associated with nearly 4-fold increase in AMI risk (odds ratio 3.87; 95% confidence interval 2.26-6.64; P <0.001), independent of other lipid levels. These data reinforce the importance of remnant cholesterol as a marker of coronary risk in this patient population.
Premature myocardial infarction is strongly associated with increased levels of remnant cholesterol.
Goliasch G, Wiesbauer F, Blessberger H et al.

Proteomic analysis highlights differences in apolipoprotein CIII association with triglycerides

Apolipoprotein C-III (apoC-III) plays a key role in regulation of triglyceride metabolism, and is therefore a potential target for therapeutic intervention. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. This study investigated the association of these different apoC-III proteoforms in 204 non-diabetic subjects. The ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in subjects who were overweight (n = 33) or obese (n = 155), compared with those with healthy weight (n=16). Moreover, fasting triglycerides were significantly correlated (p<0.001) with the ratio of apoC-III0a/apoC-III2, apoC-III0b / apoC-III2 and apoC-III1 / apoC-III2, implying that the association of apoC-III proteoforms with triglycerides appeared to be driven by apoC-III0a, apoC-III0b and apoC-III1 levels but not apoC-III2. In conclusion, the authors propose that proteomic analysis of apoC-III may provide insights into the biology of triglyceride metabolism in obesity.
The association of human apolipoprotein C-III sialylation proteoforms with plasma triglycerides.
Yassine HN, Trenchevska O, Ramrakhiani A et al.

New review focuses on management of residual risk after statin therapy

While lowering low-density lipoprotein cholesterol (LDL-C) with a statin is the cornerstone of lipid-modifying intervention to prevent cardiovascular disease, it is well recognised that a substantial residual risk of cardiovascular events persists. This review highlights evidence for other lipid abnormalities, including triglycerides, apolipoproteins and lipoprotein(a) (Lp(a)), as contributors to lipid-related residual risk. The evidence for and relative advantages and disadvantages of different therapeutic approaches targeting non-LDL abnormalities is discussed. The review also highlights a role for ezetimibe and PCSK9 inhibitors for further lowering LDL-C to reduce cardiovascular risk.
Management of residual risk after statin therapy.
Reith C, Armitage J

Media’s role in statin adherence and impact on cardiovascular risk reduction

Negative media publicity about statins has been thought to affect patient compliance with therapy. This Danish study provides support for this proposal and also shows a detrimental impact on risk for cardiovascular events. Data from 674,900 adults aged at least 40 years who started statin treatment between 1995-2010 and were followed until 31 December 2011, were evaluated. As the proportion of people on statins increased (from <1% in 1995 to 11% in 2010), early statin discontinuation trebled (from 6% in 1995 to 18% in 2010). Early statin discontinuation was associated with negative statin-related news stories (odds ratio 1.04, 95% CI 1.02-1.07); in contrast, positive news reports had a favourable effect, reducing discontinuation by 27% (odds ratio 0.73, 95% CI 0.72-0.74). Evidence that early statin discontinuation was also associated with increased risk of myocardial infarction (odds ratio 1.26, 95% CI 1.21-1.30) and death from cardiovascular disease (odds ratio 1.18, 95% CI 1.14-1.23) emphasises the need to take preventive action to optimise statin compliance and cardiovascular risk reduction.
Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study.
Nielsen SF, Nordestgaard BG