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Highlighted articles October

Volume 253 Issue October 2016

By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief).

The current issue of Atherosclerosis contains several interesting articles that investigated the effect of dietary or pharmacological interventions on cardiometabolic risk factors and diseases. The following are a selection of them.

Issue highlights

    Highlighted articles

    The relationship between the dietary inflammatory index and risk of total cardiovascular disease, ischemic heart disease and cerebrovascular disease: Findings from an Australian population-based prospective cohort study of women

    A pro-inflammatory diet based on a dietary inflammatory index (DII) was recently related to higher cardiovascular disease (CVD) risk in the general population, however, this was not investigated among women.

    Vissers and collaborators assessed the relationship between DII and risk of total CVD and CVD subgroups (myocardial infarction, ischemic heart disease, stroke and cerebrovascular disease) in a prospective cohort of 6972 Australian women aged 50–55 years at baseline in 2001.

    To this aim, the authors used clinical and procedure information from inpatient hospital separation registries, information on use of health care services, and from the causes-of-death registry to ascertain CVD outcomes during an 11-year follow-up. The association between baseline DII score and cardiovascular endpoints was studied through Cox regression analysis, with correction for demographic and cardiovascular risk factors.

    335 incident cases of CVD, 191 cases of ischaemic heart disease (including 69 myocardial infarctions) and 59 cases of cerebrovascular disease (including 40 cases of stroke) were identified. A statistically significant higher risk of myocardial infarction was observed in analyses using DII scores as a continuous variable with a hazard ratio of 1.46, but this was attenuated by further adjustment for other known cardiovascular risk factors. No association was found for total CVD, ischaemic heart diseases, or cerebrovascular disease.

    The results of the analysis indicated that, in the studied population of mid-aged Australian women, there was no statistically significant association between the dietary inflammatory index and risk of total cardiovascular disease, ischemic heart disease, myocardial infarction, cerebrovascular disease or stroke. Moreover, associations were not different for postmenopausal women.

    The lack of a clear association between DII and multiple cardiovascular and cerebrovascular endpoints is discussed in the editorial by Gambardella and Santulli who highlighted further how the results raise some concerns about the validity of expressing the diet-related inflammatory activity through DII, in different populations.

    Short-term isocaloric fructose restriction lowers apoC-III levels and yields less atherogenic lipoprotein profiles in children with obesity and metabolic syndrome

    Dietary fructose may play a role in the pathogenesis of metabolic syndrome (MetS). In a recently published study of obese children with MetS, Gugliucci and colleagues showed that isocaloric fructose restriction reduced fasting triglyceride (TG) and LDL-cholesterol (LDL-C).

    In this paper, the authors described the results of an ancillary analysis of the same study to test the hypothesis that these effects were also accompanied by improved quantitative and qualitative changes in LDL and HDL subclasses and their apolipoproteins; as well as change in VLDL, particularly apoC-III.

    Obese children with MetS consumed a diet that matched self-reported macronutrient composition for nine days, with the exception that dietary fructose was reduced from 11.7 ± 4.0% to 3.8 ± 0.5% of daily calories and substituted with glucose (in starch). Participants underwent fasting biochemical analyses on days 0 and 10. HDL and LDL subclasses were analyzed using the lipoprint HDL and LDL subfraction analysis systems from Quantimetrix.

    Significant reductions in apoB, apoC-III and apoE were observed. LDL size increased by 0.87 Å. Small dense LDL was present in 25% of the cohort and decreased by 68%. Small HDL decreased by 2.7% and large HDL increased by 2.4%. The TG/HDL-C ratio decreased from 3.1 ± 2.5 to 2.4 ± 1.4. These changes in fasting lipid profiles correlated with changes in insulin sensitivity.

    In conclusion, isocaloric fructose restriction for 9 days improved lipoprotein markers of cardiovascular risk in children with obesity and MetS. The most dramatic reduction was observed for apoC-III, which has been associated with atherogenic hypertriglyceridemia.

    In his editorial, Brinton discusses the importance of putting in place more effective measures to inform the public of both fructose content in specific foods and the potential harms of excess fructose intake, with the aim of facilitating the treatment and prevention of fructose-related health problems including dyslipidemia, central obesity, fatty liver, impaired insulin and glucose metabolism, the metabolic syndrome, diabetes mellitus, and atherosclerotic cardiovascular disease.

    Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies

    Remnant-like particle cholesterol (RLP-C) is atherogenic and may increase atherosclerotic cardiovascular disease risk. Icosapent ethyl is a high-purity prescription eicosapentaenoic acid ethyl ester, approved as an adjunct to diet, administered at 4 g/day, to reduce triglyceride (TG) levels in adult patients with TG ≥500 mg/dl. MARINE and ANCHOR are phase 3, 12-week, double-blind studies randomizing adult patients to icosapent ethyl 4 g/day, 2 g/day, or placebo. These studies showed that icosapent ethyl reduced TG and other atherogenic lipid parameter levels without increasing low-density lipoprotein cholesterol (LDL-C) levels.


    In their exploratory analysis, Ballantyne and colleagues took advantage of MARINE and ANCHOR to evaluate the effects of icosapent ethyl on calculated and directly measured RLP-C.


    By immunoseparation assay, the authors assessed median percent change of RLP-C levels from baseline to study end and calculated RLP-C levels in the full populations.


    The results of the analysis showed that icosapent ethyl 4 g/day significantly reduced directly measured RLP-C levels (−29.8% in MARINE and −25.8% in ANCHOR) versus placebo, and also reduced directly measured RLP-C levels to a greater extent in subgroups with higher versus lower baseline TG levels, in patients receiving statins versus no statins (MARINE), and in patients receiving medium/higher-intensity versus lower-intensity statins (ANCHOR). Strong correlations were found between calculated and directly measured RLP-C for baseline, end-of-treatment, and percent change values in ANCHOR and MARINE.


    In conclusion, icosapent ethyl 4 g/day significantly reduced calculated and directly measured RLP-C levels versus placebo in patients with elevated TG levels from the MARINE and ANCHOR studies.

    Impact of statin therapy on plasma adiponectin concentrations: A systematic review and meta-analysis of 43 randomized controlled trial arms

    The effect of statin therapy on plasma adiponectin levels has not been conclusively studied.

    Chruściel and colleagues therefore aimed to evaluate this effect through a systematic review and meta-analysis of available randomized controlled trials (RCTs).

    Quantitative data synthesis was performed using a random-effects model with weighted mean difference (WMD) and 95% confidence interval as summary statistics.

    The results of the analysis showed that in 30 studies (43 study arms) with 2953 participants, a significant increase in plasma adiponectin levels was observed after statin therapy. In subgroup analysis, atorvastatin, simvastatin, rosuvastatin, pravastatin and pitavastatin were found to change plasma adiponectin concentrations by 0.70 μg/ml, 0.50 μg/ml, −0.70 μg/m, 0.62 μg/ml, and 0.51 μg/ml, respectively. With respect to treatment duration, there was a significant increase in the subset of trials lasting ≥12 weeks but not in the subset of <12 weeks of duration. Random-effects meta-regression suggested a significant association between statin-induced elevation of plasma adiponectin and changes in plasma low density lipoprotein cholesterol levels.

    This meta-analysis showed a significant increase in plasma adiponectin levels following statin therapy. Although statins are known to increase the risk for new onset diabetes mellitus, these data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression.

    In their editorial, Katsiki and Mantzoros describe how both statins and adiponectin share several beneficial effects on oxidative stress, inflammation, endothelial dysfunction, atherosclerosis and thrombosis, thus reducing cardiovascular risk. Furthermore, adiponectin regulates glucose and lipid metabolism. Future research is needed to establish the causality, if any, of the observed association between statins and adiponectin.

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