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Atherosclerosis Journal Highlights September 2016

28 September 2016   (0 Comments)
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Volume 252 Issue September 2016

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

This issue of Atherosclerosis contains four original articles on the course and management of familial hypercholesterolemia (FH), which has recently attracted increased scientific and clinical interest since it is more frequent than previously thought, underdiagnosed and undertreated. In addition, the results of FH research have generated new therapeutic targets and drugs for the treatment of dyslipidemia and prevention of atherosclerosis.

Issue highlights

    Highlighted articles

    Prevalence of potential familial hypercholesteremia (FH) in 54,811 statin-treated patients in clinical practice

    Familial hypercholesterolemia (FH) is a life-threatening disease, characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and a premature, increased risk of coronary heart disease (CHD) that is globally underdiagnosed.

    Catapano et al. assessed the percentage of patients with possible or probable FH in various countries, by analyzing a population previously reported in the Dyslipidemia International Study (DYSIS), a multinational, cross-sectional observational study of 54,811 adult outpatients treated with statin therapy. The percentage of patients with high levels of LDL-C and with possible or probable FH was determined, across 29 countries, using the Dutch scoring method for FH, in age subgroups for the analysis population and among diabetes patients.

    The authors showed that despite statin therapy, 16.1% of patients had high LDL-C levels (>3.6 mmol/L) and the prevalence of possible and probable FH was 15.0% and 1.1%, respectively. The highest percentages of probable FH occurred in Egypt (5.4%), the Baltic states (4.2%), Russia (3.2%), and Slovenia (3.1%), with the lowest rates in Israel (0.0%), Canada (0.2%), and Sweden (0.3%). FH rates were the highest in younger patients (45–54 years) for secondary prevention, regardless of the presence/absence of diabetes, and more than 60% of patients with probable FH had CHD.

    Earlier diagnosis and treatment of patients with FH are needed to reduce CHD risk in these patients.

    Dietary counseling is associated with an improved lipid profile in children with familial hypercholesterolemia

    In patients diagnosed with familial hypercholesterolemia (FH), guidelines recommend cholesterol-lowering medication from 8 to 10 years of age and dietary recommendations. Little is known about the diet of FH children and the effect of dietary counselling.

    Torvik et al. aimed at describing the diet of FH children with respect to fat quality and to investigate whether dietary counseling improved lipid profile. To this purpose, fifty-four FH children (5–18 years) were included in the study and dietary intake was recorded with a pre-coded food diary for four days. Information about plasma lipid levels was obtained.

    The authors showed that median intake of total fat, monounsaturated fat, polyunsaturated fat (PUFA) and saturated fat (SFA) was 30.8, 10.4, 5.9 and 12.0 E%, respectively. Among non-statin treated FH children, SFA intake was significantly correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) B, and PUFA/SFA ratio was significantly inversely correlated with TC. Compared to the first visit, non-statin and non-plant sterol treated FH children had significantly reduced levels of TC, LDL-C, high-density lipoprotein cholesterol, apo B and apo A-1, at a later visit.

    In conclusions, FH children had a higher intake of SFA than recommended and the SFA intake was positively correlated with plasma TC, LDL-C and apo B levels in FH children not using statins. Importantly, the plasma lipid profile was improved in FH children after dietary counseling, where focus was put on reduction of SFA intake and dietary cholesterol.  

    Angiographic progression of coronary atherosclerosis in patients with familial hypercholesterolaemia treated with non-statin therapy: Impact of a fat-modified diet and a resin

    Familial hypercholesterolaemia (FH) profoundly increases the risk of coronary artery disease (CAD).

    Watts et al. investigated whether diet and a bile-acid sequestrant decrease coronary atherosclerosis in patients with FH. The authors identified 26 men with FH and CAD, participating in the St Thomas' Atherosclerosis Regression Study, who had been randomized to receive a fat-modified diet plus cholestyramine (DC) or usual care (UC), and investigated the relative effects of these treatments on the angiographic progression of coronary atherosclerosis over 39 months. FH was defined as probable/definite according to Dutch Lipid Clinic Network criteria; mean FH score was 8.7 and mean baseline low-density lipoprotein cholesterol (LDL-Ch) concentration was 5.4 mmol/L. Coronary atherosclerosis was assessed by serial quantitative angiography, as the global changes in mean and minimum absolute width of segments (MAWS and MinAWS, respectively).

    The results show that mean plasma LDL-Ch concentration fell by 35% in the DC group and remained significantly lower during the trial compared with the UC group (3.78 mmol/L vs. 4.89 mmol/L). MAWS decreased by 0.252 mm in the UC group and by 0.001 mm in the DC group, with corresponding reductions in MinAWS of 0.290 mm and 0.013 mm; these changes were significant after adjusting for baseline variables, including coronary luminal dimensions and lipoprotein (a). Progression was observed in 7 patients on UC and 3 on DC, with regression in no patients and 3 patients, respectively.

    This investigation demonstrates that a prudent diet and cholestyramine could improve the course of coronary atherosclerosis in men with phenotypic FH through sustained reductions in LDL-Ch. 

    Knowledge gaps in the management of familial hypercholesterolaemia. A UK based survey

    Untreated individuals with familial hypercholesterolaemia (FH) are at increased risk of developing premature cardiovascular disease (CVD). Early diagnosis and treatment can result in a normal life expectancy. A recent survey commissioned by the European Atherosclerosis Society (EAS) reported a lack of awareness of FH in the general population.

    Based on this observation, Schofield et al. conducted a survey to assess knowledge of diagnostic criteria, risk assessment, the role of cascade screening, and management options for patients with FH among healthcare professionals involved in the assessment and management of cardiovascular risk and disease in the United Kingdom. The survey was distributed to 1000 healthcare professionals. The same survey was redistributed following attendance at an educational session on FH.

    The authors showed that 151 respondents (40.5%) reported having patients under their care who would meet the diagnostic criteria for FH, but just 61.4% recognized that cardiovascular risk estimation tools cannot be applied in FH, and only 22.3% understood the relative risk of premature CVD compared to the general population. Similarly, just 65.9% were aware of recommendations regarding cascade screening. Following education, more healthcare providers recognized that there were patients under their care who would satisfy the diagnostic criteria (48.4%), and participants were significantly more likely to recognize that treatment should not be guided by cardiovascular risk estimation (85.3%), as LDL-C is raised from birth, resulting in a 20-fold increased risk of premature CVD.

    It can be concluded that the prevalence and associated risk of FH continue to be underestimated, and knowledge of diagnostic criteria and treatment options is suboptimal. These results support the recent Consensus Statement of the EAS and production of quality standards by the National Institute for Health and Care Excellence. Further work is required to formulate interventions to improve FH awareness and knowledge, and to determine the effect these interventions have on patient outcomes.

    In the accompanying editorial, Roeters van Lennep emphasized the evidence that essential knowledge about FH is still lacking and the risk of premature CVD is significantly underestimated and highlighted the fact that education helps, since after the educational session, health care professionals recognized that they had more patients under their care that would meet the diagnostic criteria (even though the sample of health care professionals who filled in a second questionnaire following the educational session was small (n=35)). Therefore, it is worth investing in educational programs on FH for a wide array of health care professionals.

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