Atherosclerosis

Achilles tendon ultrasonography – A useful screening tool for cardiovascular risk estimation in patients with severe hypercholesterolemia Publication date: March 2019 Source: Atherosclerosis Supplements, Volume 36 Author(s): Sandra Kutkienė, Žaneta Petrulionienė, Aleksandras Laucevičius, Rimantė Čerkauskienė, Artūras Samuilis, Virginija Augaitienė, Aurelija Gedminaitė, Gintarė Bieliauskienė, Akvilė Šaulytė-Mikulskienė, Justina Staigytė, Emilija Petrulionytė, Urtė Gargalskaitė, Eglė Skiauterytė, Gabija Matuzevičienė, Milda Kovaitė, Irena Nedzelskienė Abstract Background and aims Achilles tendon lesions have long been associated with genetic defects in lipid metabolism and increased risk of cardiovascular diseases (CVD). With this study we aimed to evaluate the usefulness of Achilles tendon ultrasonography in identifying people at greater risk among subjects with severe hypercholesterolemia (SH) in a high-risk population. Methods During the period of 2016–2017 a total of 213 participants were enrolled in this case-control study. Data of 110 patients with SH and 103 age and sex matched controls without dyslipidaeplemia and established CVD was collected. Results Achilles tendinopathy (AT) was present in 42.7% of subjects with SH and in 29.1% of controls (p = 0.039). Stronger association between SH and AT was seen in women – 24.1% vs 2.0% (p = 0.001). SH increased odds of AT by 1.815 (95% CI, 1.028–3.206). Prevalence of AT was higher in males despite presence (SH+) or absence (SH−) of severe hypercholesterolemia (SH+ 60.7% vs 24.1%, SH− 55.8% vs 2.0%, p < 0.001). AT was associated with higher proportion of subjects exceeding normal mean values of TC (80.5% vs 52.9%, p = 0.001), LDL-C (76.6% vs 52.2%), TG (54.5% vs. 22.1%), ApoB (57.1% vs 22.2%), ApoE (44.0% vs 22.4%) levels and ApoB/ApoA ratio (46.1% vs 21.5%) (p = 0.001) and family history of premature coronary heart disease (CHD). Conclusions AT is more prevalent among subjects with SH and is associated with higher levels of TC, TG, LDL-C, ApoB, ApoE, ApoB/ApoA ratio, family history of premature CHD. SH increases the odds of developing AT.

Investigating the association between familial hypercholesterolemia and perceived depression Publication date: March 2019 Source: Atherosclerosis Supplements, Volume 36 Author(s): Nien-Tzu Chang, Ta-Chen Su Abstract Background and aims Inherited familial hypercholesterolemia (FH) increases cardiovascular risks, but perceived depression in FH is unknown. This study aims to explore the association between the FH and perceived depression. Methods This study was a hospital-based design, we started to recruit clinical diagnosis of phenotypic FH since 2014 for the Ten Countries Study in the Asia-Pacific region. We consecutively recruited 302 FH patients and other 414 comparison subjects (214 subjects with hypertriglyceridemia and 200 subjects with normal lipid controls) from the special lipid clinic of National Taiwan University Hospital, Taipei. All participants received cardiovascular health examinations and completed a self-reported questionnaire, including the Center for Epidemiologic Studies Depression Scale (CES-D) for assessment of the psychosocial depression. Results Clinical FH patients had a higher risk of perceived depression, with an odds ratio (95% confidence intervals) of possible depression by 1.50 (1.07–2.11) and probable depression by 1.73 (1.10–2.75) than those of the non-FH groups after adjusted relevant cardiovascular risk factors. FH patients with a family history of coronary heart disease (CHD) had higher domain-specific depression scores than those of controls. In addition, this study found that FH patients with lower educational levels also had a higher risk of depression compared with those in control groups. Conclusions Patients with clinical phenotype of FH are associated with subjectively perceived depression, particularly among FH patients with a family history of CHD. Graphical abstract

Establishing a familial hypercholesterolaemia register - The first year Publication date: March 2019 Source: Atherosclerosis Supplements, Volume 36 Author(s): Myra Tilney Abstract Background and aims Familial hypercholesterolemia (FH) is an autosomal dominant condition raising the risk of premature cardiovascular disease up to twentyfold.[1] [2] It is under-diagnosed and undertreated, in spite of availability of effective treatment. Registers are recommended to assist in the recognition and improvement of the condition since treatment reduces morbidity and mortality. Disease registers enable longitudinal review and the application of continuous quality improvement methodology. The aims of this paper are to describe the process of setting up a new FH register in Malta based on phenotype, the preliminary results achieved, the barriers encountered, how these were overcome, and future plans for development. Methods The registry was established as an observational clinical study designed for a small healthcare system with limited resources. Effective process design requires attention to standards, capacity, outcome measurement and feedback, which have been incorporated. Results 43 individuals have been registered applying Dutch Lipid Clinic Network standards, including 9 Definite, 16 Probable and 18 Possible FH. Cascade testing has identified three younger, and one older FH individuals; amenable risk factors and target outcomes are available for feedback and action. Barriers included insufficient infrastructure, limited stakeholder involvement, time limitations impacting clinical care and data collection, poor recognition, awareness and referral, and limited cascade testing. Overcoming these required persistence, reorganizing clinical work, with some assistance from clinic nurses, forward planning to involve patients and raising FH awareness through presentations to various audiences. Conclusions During this year the register was established and is functional: awareness is being raised. Future steps will target process improvement for effectiveness and sustainability.

Percutaneous coronary intervention for a Chinese familial hypercholesterolemia homozygous under the guidance of optical coherence tomography Publication date: March 2019 Source: Atherosclerosis Supplements, Volume 36 Author(s): Zesen Liu, Jie Peng, Shilong Wang, Tao Jiang, Weicong Zhang, Chun Zhang, Yan Chen, Kang Meng, Jie Lin Abstract Homozygous familial hypercholesterolemia developed into severe cardiovascular consequences early. Untreated HoFH usually cannot survive over 30 years old. Acute coronary syndrome(ACS) caused by plaque rupture is one of the main causes of death in HoFH. As the highest resolution intravascular imaging technique, optical coherence tomography(OCT) can clearly show the thickness and structural characteristics of atherosclerotic plaque caps. In this study, a Chinese male HoFH received percutaneous coronary intervention for unstable angina. After analyzed his genetic and follow-up data, OCT was performed during interventional therapy. Multiple lipid rich plaques accompanied with inflammatory cell infiltration and a thin-cap fibroatheroma(TCFA) were noted, which reflected the vulnerability of plaques. The utility of OCT had certain guiding significance for strategy of interventional therapy and the long-term drug management. And this case suggested that it was important to undergo OCT examination for patients with HoFH who required percutaneous coronary intervention.

Familial hypercholesterolemia in China half a century: A review of published literature Publication date: March 2019 Source: Atherosclerosis Supplements, Volume 36 Author(s): Jie Peng, Xue Wu, Shilong Wang, Shuang Zhang, Xumin Wang, Zesen Liu, Jing Hong, Pucong Ye, Jie Lin Abstract Aims To investigate the status of familial hypercholesterolemia (FH) research and the characteristics of patients with FH in China. Methods Published papers in Chinese or English language from PubMed, SinoMed and CNKI databases from 1971 to March 2018 were searched using 'Familial hypercholesterolemia', 'Chinese' and 'Han' as keywords. A systematic review of studies on familial hypercholesterolemia was then conducted. Results A total of 391 articles were found, in which 22% were in English and 78% were in Chinese; approximately 43% are case reports and 34% are genetic reports according to the study type; 52% discussed the status of the disease and 11% investigated the subclinical status according to the study content. Furthermore, 96% of the articles were published by tertiary hospitals and 46% were conducted by cardiologists. The first expert consensus was issued in February 2018. Of the 163 case reports published before 2018, 48.7% used the Chinese FH clinical diagnostic criteria and 34.4% did not clearly indicate the diagnostic criteria. The incidence rates of low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) mutations were 82% and 9%, and proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations were rare in Chinese patients with FH. However, the data on lipid-lowering treatment rates, compliance rates and cardiovascular events in FH remain insufficient. Conclusions Large-scale epidemiological investigation of FH has not been demonstrated, the recognition of FH remains rudimentary, and the guidelines are incomplete in China. The diagnosis and management of Chinese FH needs to be improved.

Variable expression and penetrance in Portuguese families with Familial Hypercholesterolemia with mild phenotype Publication date: March 2019 Source: Atherosclerosis Supplements, Volume 36 Author(s): I.M. Gaspar, A. Gaspar Abstract Familial hypercholesterolemia is an Mendelian dominant disorder characterized by defects of the low density lipoprotein receptor (LDLR) that result in a defective removal of LDL from plasma, which promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and arteries (atherosclerosis). Diagnosis severe clinical phenotype FH with Dutch Lipid Clinic Network Criteria, encompassing history of premature ASCVD, tendon xanthomas, and a family history of hypercholesterolemia and premature ASCVD in relatives is rare in the Portuguese FH patients. There is a variability of the phenotype in FH individuals with clinical diagnosis or genetic mutation (carriers and patients) probably due to environmental factors in the last century, a Mediterranean diet, or a diet without fat food, trans fat food, no smoking, no sedentary life that can interfere with our metabolism, or are consequences of polygenic, epigenetic, acquired defects, modifiers genes and beta-globin asymptomatic carriers. We have several concepts/mechanisms in genetics that are transversal to hereditary diseases and common in FH, such as somatic mosaicism, germinal mosaicism, variable expression and variable penetrance of mutations. A negative blood genetic test result does not exclude FH, because the pathogenic LDLR mutation can be expressed only in the liver (a mutation in somatic tissue) or occasionally there is a vertical transmission from partner to future child by a mutation on germinal line - germinal mosaicism. Unlike north European countries, the most FH carriers and patients had less severe phenotypes, for example with have children and young adult carriers with LDL-R mutation had normal TC and LDL-C, old women had a milder phenotype without ASCVD events, tendon xanthomas are seen in <1% patients, and most homozygous FH patients are under combined therapy.

The frequency of familial hypercholesterolemia amongst patients in the outpatient clinic of the tertiary specialized cardiology center in Kyrgyzstan Publication date: March 2019 Source: Atherosclerosis Supplements, Volume 36 Author(s): O.S. Lunegova, A.E. Mirrakhimov, E. Hodzhiboboev, E.E. Bektasheva, K.V. Neronova, U.M. Toktomamatov, U. Zakirov, A. Asanbaev, R.A. Arapova, S.S. Abilova, A.S. Kerimkulova, E.M. Mirrakhimov Abstract Background Familial hypercholesterolemia (FH) is frequently underdiagnosed. Prevalence of the FH in Kyrgyzstan is unknown. Aim to investigate the prevalence of FH amongst patients in the outpatient settings of the tertiary cardiologic center in Kyrgyzstan. Methods Retrospective observational study was conducted using the database of the laboratory of biochemistry and electronic database of outpatient department of the National Center of Cardiology and internal diseases. Patient with the level of total cholesterol (TC) ≥7,5 mmol/l and/or low density lipoprotein cholesterol (LDL-C) ≥ 4,9 mmol/l without signs of secondary hyperlipidemia were included in the analysis. FH was defined using Dutch Lipid Clinic Network criteria. Results according to the laboratory database levels of TC and LDL-C was conducted in 8281patiens and 525 of them had a high lipid levels. After exclusion of patients with secondary hyperlipidemia, high level of triglycerides and pregnant women – 91 patients were included in the analysis. Among them the definite FH was revealed in 2 (2,2%) patients, probable FH - in 6 (6,6%), and possible in 76 (83,5%), and in 7,7% there were no signs of FH. Conclusion Frequency of potential FH (definite and probable) in our analysis was low. To understand the real prevalence of FH in a Kyrgyz population epidemiological study is needed.

Epidemiology of cardiovascular risk factors in two population-based studies Publication date: September 2018 Source: Atherosclerosis Supplements, Volume 35 Author(s): Elena Olmastroni, Evgeny V. Shlyakhto, Aleksandra O. Konradi, Oxana P. Rotar, Asiiat S. Alieva, Maria A. Boyarinova, Andrea Baragetti, Liliana Grigore, Fabio Pellegatta, Elena Tragni, Alberico L. Catapano, Manuela Casula Abstract We aimed to compare cardiovascular risk factors prevalence in Italy and Russia through cross-sectional database analysis. The study has been based on data from ESSE-RF and from baseline of PLIC study, two population-based epidemiological studies aimed to investigate prevalence of risk factors and evaluating contribution of traditional and new risk factors into morbidity and cardiovascular mortality. A total of 2203 patients with left and right intima-media thickness (IMT) measurements constituted the source population (1205 from PLIC study and 998 from ESSE-RF study). Sample of ESSE-RF study had slightly more diabetic and hypertensive individuals, while the percentage of subjects with high cholesterol value was lower than in the other sample (67.1% vs 79.9%). The median LDL-C value was higher among individuals not treated with statins in the PLIC sample (p < 0.001), while was comparable among subjects receiving statin therapy. On the other hand, the percentage of individuals with positive cardiovascular history was higher in ESSE-RF sample. This could also explain the higher mean IMT value (0.71 ± 0.17 vs 0.63 ± 0.13) in the whole sample, and among patients without past cardiovascular events (regardless of statin treatment), despite some differences in major risk factors. Despite Russian and Italian populations are culturally and geographically different, they are not so different based on characteristics analyzed.

Notch, BMP and WNT/β-catenin network is impaired in endothelial cells of the patients with thoracic aortic aneurysm Publication date: September 2018 Source: Atherosclerosis Supplements, Volume 35 Author(s): Aleksandra Kostina, Hanna Bjork, Elena Ignatieva, Olga Irtyuga, Vladimir Uspensky, Daria Semenova, Shohreh Maleki, Alexey Tomilin, Olga Moiseeva, Anders Franco-Cereceda, Mikhail Gordeev, Giuseppe Faggian, Anna Kostareva, Per Eriksson, Anna Malashicheva Abstract Cellular and molecular mechanisms of thoracic aortic aneurysm are still not clear and therapeutic approaches are mostly absent. The role of endothelial cells in aortic wall integrity is emerging from recent studies. Although Notch pathway ensures endothelial development and integrity, and NOTCH1 mutations have been associated with thoracic aortic aneurysms, the role of this pathway in aneurysm remains elusive. The purpose of the present work was to study functions of Notch genes in endothelial cells of patients with sporadic thoracic aortic aneurysm. Aortic endothelial cells were isolated from aortic tissue of patients with thoracic aortic aneurysm and healthy donors. Gene expression of Notch and related BMP and WNT/β-catenin pathways was estimated by qPCR; WNT/β-catenin signaling was studied by TCF-luciferase reporter. To study the stress-response the cells were subjected to laminar shear stress and the expression of corresponding genes was estimated by qPCR. Analyses of mRNA expression of Notch genes, Notch target genes and Notch related pathways showed that endothelial cells of aneurysm patients have dysregulated Notch/BMP/WNT pathways compared to donor cells. Activity of Wnt pathway was significantly elevated in endothelial cells of the patients. Cells from patients had attenuated activation of DLL4, SNAIL1, DKK1 and BMP2 in response to shear stress. In conclusion endothelial cells of the patients with thoracic aortic aneurysm have dysregulated Notch, BMP and WNT/β-catenin related signaling. Shear stress-response and cross-talk between Notch and Wnt pathways that normally ensures aortic integrity and resistance of endothelial cells to stress is impaired in aneurysmal patients.

Large artery stiffness according to different assessment methods in adult population of St.Petersburg Publication date: September 2018 Source: Atherosclerosis Supplements, Volume 35 Author(s): A.S. Alieva, O.P. Rotar, A.V. Orlov, M.A. Boyarinova, E.V. Moguchaya, A.N. Rogoza, A.O. Konradi, E.V. Shlyakhto Abstract Objective The aim of the present study was to assess the prevalence of increased arterial stiffness by different diagnostic methods and its association with cardiovascular risk in Russian population-based cohort. Design and methods In terms of Russian epidemiological study ESSE-RF a random selection of 452 apparently healthy Saint-Petersburg inhabitants aged 25–65 years was performed. Fasting lipids, glucose and blood pressure measurements were performed. We used 3 diagnostic methods of arterial stiffness assessment: pulse wave velocity by applanation tonometry (SphygmoCor - PWV-S) and pulse wave velocity by volumetric sphygmography (VaSera - PWV-V), and cardio-ankle vascular index (CAVI) by VaSera. Results 341 (75,4%) had normal parameters of arterial stiffness assessed by all methods. Spearmen's coefficient of correlation and "kappa" coefficient for PWV-S and CAVI were 0,74 and 0,04, for PWV-S and PWV-V - 0,10 and 0,06, for CAVI and PWV-V - 0,28 and 0,03, respectively. There was a significant correlation between cardiovascular risk (defined by SCORE) and PWV-S (r = 0,38, p < 0,001) and a non-significant trend of increasing CAVI along with cardiovascular risk (r = 0,35, p = 0,14). Conclusions Different methods of arterial stiffness assessment showed a weak correlation with each other. Carotid-femoral pulse wave velocity detected by applanation tonometry is associated with high cardiovascular risk score and might be considered as better additional risk marker for cardiovascular risk stratification.

Alexandros Sfakianakis
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alsfakia@gmail.com