International Atherosclerosis Society Research Articles

Impact of the severe familial hypercholesterolemia status on atherosclerotic risks

Abstract Backgrounds Risks of atherosclerotic events substantially vary even among patients with familial hypercholesterolemia (FH) with extremely high risk based on life-long exposure to high low-density lipoprotein cholesterol levels. Purpose This study aimed to examine the impact of the severe FH status defined by the International Atherosclerosis Society (IAS). Methods Data of patients with FH (N = 1,050, male = 490) who were admitted to our university hospital between 2000 and 2020 and who were followed up were retrospectively reviewed. The number of major adverse cardiac events (MACEs), including mortality associated with cardiovascular disease, acute coronary syndrome, and ischemic heart disease requiring coronary revascularization per 1,000 person-years, was calculated. Hazard ratio was also calculated using Cox proportional model. Results Overall, 545 (51.9%) patients had severe FH. The median follow-up duration was 12.6 years. In total, 171 MACEs were recorded during the follow-up period. Severe FH was significantly associated with MACE (hazard ratio = 6.48, 95% confidence interval = 2.56–10.40, P < 0.001). The event rates per 1,000 person-years in the primary prevention group of non-severe FH and severe FH, were 0.0 and 15.6, respectively. The event rates per 1,000 person-years in the secondary prevention group of non-severe FH and severe FH, were 2.0 and 32.3, respectively. Conclusions Patients with severe FH exhibited significantly higher risks in primary and secondary prevention settings. This simple criterion provides useful information for identifying patients with even higher risk who may need further management.

Application of implementation science for improving the utilization of an international clinical practice guidance on familial hypercholesterolemia

The International Atherosclerosis Society (IAS) published an evidence-informed guidance for familial hypercholesterolemia (FH) that provides both clinical and implementation recommendations. We reference examples of strategies from the literature to explore how these implementation recommendations can be tailored into implementation strategies at the local-level for stakeholders guided by a framework proposed by Sarkies and Jones. Four authors of the IAS guidance selected two published exemplar implementation recommendations for detection, management, and general implementation. Each recommendation was described as an implementation strategy using Proctor's guidance for specifying and reporting implementation strategies. It recommends reporting the actor (who), action (what), action-target (who is impacted), temporality (how often), and dose (how much) for each implementation strategy. Detection: A centralized cascade testing model, mobilized nurses (actor) to relative's homes, after the diagnosis of the proband (temporality), once (dose) to consent, obtain a blood sample and health information (action) on relatives (action-target). A primary care initiative to improve FH management included an educational session (action) with clinicians (action-target), computer-based reminder message and message to patients to have their cholesterol screened once (dose) at a visit or outreach (temporality) by researchers (actor). General: A partnership between a statewide public pathology provider, local public hospital network, primary health network, government health ministry, and an academic university (actors) was established to implement a primary-tertiary shared care model (action) to improve the detection of FH (action-target). We demonstrate that implementation recommendations can be specified and reported for different local contexts with examples on monitoring, evaluation, and sustainability in practice.

International Atherosclerosis Society Roadmap for Familial Hypercholesterolaemia.

Familial hypercholesterolaemia (FH), a common monogenic disorder, is a preventable cause of premature coronary artery disease and death. Up to 35 million people worldwide have FH, but most remain undetected and undertreated. Several clinical guidelines have addressed the gaps in care of FH, but little focus has been given to implementation science and practice. The International Atherosclerosis Society (IAS) has developed an evidence-informed guidance for the detection and management of patients with FH, supplemented with implementation strategies to optimize contextual models of care. The guidance is partitioned into detection, management and implementation sections. Detection deals with screening, diagnosis, genetic testing and counselling. Management includes risk stratification, treatment of adults and children with heterozygous and homozygous FH, management of FH during pregnancy, and use of lipoprotein apheresis. Specific and general implementation strategies, guided by processes specified by the Expert Recommendations for Implementing Change taxonomy, are provided. Core generic implementation strategies are given for improving care. Nation-specific cholesterol awareness campaigns should be utilized to promote better detection of FH. Integrated models of care should be underpinned by health policy and adapted to meet local, regional and national needs. Clinical centres of excellence are important for taking referrals from the community. General practitioners should work seamlessly with multidisciplinary teams. All health-care providers must receive training in essential skills for caring for patients and families with FH. Management should be supported by shared decision-making and service improvement driven by patient-reported outcomes. Improvements in services require sharing of existing resources that can support care. Advocacy should be utilized to ensure sustainable funding. Digital health technologies and clinical quality registries have special value. Finally, academic-service partnerships need to be developed to identify gaps in care and set priorities for research. This new IAS guidance on FH complements the recent World Heart Federation Cholesterol Roadmap.

Impact of the severe familial hypercholesterolemia status on atherosclerotic risks

Risks of atherosclerotic events substantially vary even among patients with familial hypercholesterolemia (FH) with extremely high risk based on life-long exposure to high low-density lipoprotein cholesterol levels. This study aimed to examine the impact of the severe FH status defined by the International Atherosclerosis Society (IAS). Data of patients with FH (N = 1050, male = 490) who were admitted to Kanazawa University Hospital between 2000 and 2020 and who were followed up were retrospectively reviewed. The number of major adverse cardiac events (MACEs), including mortality associated with cardiovascular disease, acute coronary syndrome, and ischemic heart disease requiring coronary revascularization per 1000 person-years, was calculated. Hazard ratio was also calculated using Cox proportional model. Overall, 545 (51.9%) patients had severe FH. The median follow-up duration was 12.6 years. In total, 171 MACEs were recorded during the follow-up period. Severe FH was significantly associated with MACE (hazard ratio = 6.48, 95% confidence interval = 2.56–10.40, P = 1.2 × 10−5). The event rates per 1000 person-years in the primary prevention group of non-severe FH and severe FH, were 0.0 and 15.6, respectively. The event rates per 1000 person-years in the secondary prevention group of non-severe FH and severe FH, were 2.0 and 32.3, respectively. Patients with severe FH exhibited significantly higher risks in primary and secondary prevention settings. This simple criterion provides useful information for identifying patients with even higher risk who may need further management.

Abstract 11402: Impact of the Severe Familial Hypercholesterolemia Status on Atherosclerotic Risks

Background and aims: Risk of atherosclerotic events substantially vary even among patients with familial hypercholesterolemia (FH) with extremely high risk based on life-long exposure to elevated LDL cholesterol. We aimed to examine impact of the severe FH status defined by the International Atherosclerosis Society (IAS). Methods: The data of patients with FH (N = 1,050, male = 490) who were admitted to Kanazawa University Hospital between 2000 and 2020 and who were followed-up were retrospectively reviewed. The number of MACEs, including mortality associated with cardiovascular disease, acute coronary syndrome, and ischemic heart disease requiring coronary revascularization per 1,000 person-years, was calculated. In addition, hazard ratio was calculated using Cox proportional model. Results: Overall, we identified 545 patients (51.9 %) with severe FH in this population. The median follow-up duration was 12.6 years. In total, 171 MACEs were recorded during the follow-up period. We found that severe FH was significantly associated with MACE (hazard ratio = 6.48, 95% confidence interval = 2.56 - 10.40, P = 1.2 х 10 -5 ). The event rates per 1,000 person-years for in the primary prevention group (non-severe FH and severe FH) were 0.0 and 15.6, respectively. The event rates per 1,000 person-years in the secondary prevention group (non-severe FH and severe FH) were 2.0 and 32.3, respectively. Conclusion: Patients with severe FH exhibited significant higher risks in primary as well as secondary prevention settings. This simple criterion provides us useful information to identify patients with even higher risk who may need further managements.

To survey on the components of metabolic syndrome and determine the serum ferritin levels in patients with metabolic syndrome

Background: Metabolic syndrome is one of the most common public health concerns in the 21st century. Several studies in the world have shown a link between elevated serum ferritin and metabolic syndrome as well as the risk of metabolic syndrome, the study provides a number of conclusions argues that ferritin may be considered as an early predictor of metabolic syndrome. For that reason, we conducted this study with the objective: “To survey on the components of metabolic syndrome and determine the serum ferritin levels in patients with metabolic syndrome”. Methods: A descriptive, cross-sectional study on 207 patients who were treated at the General Internal Medicine-Geriatric Department, Hue Central Hospital from 5/2016 to 8/2017. Patients were divided into two groups: study group (104 patients with metabolic syndrome) and control group (103 patients without metabolic syndrome and no serum ferritin-mediated disease). The metabolic syndrome was diagnosed by joint interim statement of the International Diabetes Federation/American Heart Association/ National Heart, Lung, and Blood Institute/ World Heart Federation/ International Atherosclerosis Society/ International Association for the Study of Obesity 2009. Results: The most common combination of metabolic syndrome components was: hypertriglyceridemia - hypertension - hyperglycemia (15.1%). In the metabolic syndrome group, mean serum ferritin concentration was 391.62±181.97ng/ml (Increased ferritin concentration accounted for 86.54%). In men, mean serum ferritin concentration was 453.064 ± 161.75ng/ml (Increased ferritin concentration accounted for 96.15%). In women, mean serum ferritin concentration was 330.17 ± 181.71 ng/ml (Increased ferritin concentration accounted for 86.54%). Conclusion: In the group of patients with metabolic syndrome, the serum ferritin levels increases and the rate of Increased ferritin concentration was high.

Efficacy and safety of bempedoic acid in patients with and without metabolic syndrome: Pooled analysis of data from four phase 3 clinical trials

Background and aimsBempedoic acid significantly lowers low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia but its effects in patients with metabolic syndrome (MetS) have not been well characterized. We sought to determine the efficacy and safety of bempedoic acid in patients with hypercholesterolemia by baseline MetS status. MethodsThis study used pooled data from four phase 3 studies. Using modified International Atherosclerosis Society guidelines, patients were grouped into two pools: those with and those without MetS. Patients with diabetes were excluded. Endpoints assessed change from baseline to week 12 in lipid and glycemic parameters and high-sensitivity C-reactive protein (hsCRP), and safety. ResultsThe study included 936 patients with MetS (bempedoic acid, 648; placebo, 288) and 1573 without MetS (bempedoic acid, 1037; placebo, 536). Significant placebo-corrected reductions in LDL-C were observed with bempedoic acid (p < 0.0001), with a slightly larger decrease in patients with vs. without MetS (−22.3% vs. −18.4%; interaction p = 0.0472). Compared with placebo, bempedoic acid significantly (p < 0.0001) lowered total cholesterol, non–high-density lipoprotein cholesterol, apolipoprotein B, and hsCRP, with a similar magnitude of benefit observed between MetS categories. Triglycerides increased with bempedoic acid but only to a lesser extent than with placebo in patients without MetS (placebo-corrected difference, −4.4%; p = 0.02). Only patients with MetS experienced decreases in glycated hemoglobin (−0.07%; p < 0.0001) and fasting plasma glucose (−2.4 mg/dL; p = 0.002). Safety was comparable between MetS categories and treatment groups. ConclusionsThese data suggest that bempedoic acid is a suitable therapy for patients with and without MetS who require additional lipid lowering.

International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia.

This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. FH,a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.

METABOLIC SYNDROME IN PATIENTS WITH ANDROGENETIC ALOPECIA IN A TERTIARY CARE HOSPITAL

Background: Androgenetic alopecia (AGA) is a hereditary androgen-dependent disorder, characterized by a progressive decline in hair fibre production by scalp hair follicles and their eventual miniaturization. Metabolic syndrome is a cluster of inter-related risk factors that increase the risk of coronary artery disease. Despite the high burden of Androgenetic Alopecia and Metabolic Syndrome in India, specific data on the participants are relatively sparse.&#x0D; &#x0D; Methods: A total of 126 patients of androgenetic alopecia (age range 18-55 years; mean age 30.83±10.37 years; 83.3% males) falling in sampling frame were enrolled in the study and were assessed clinically, anthropometrically and biochemically. Metabolic syndrome was diagnosed using Joint interim statement of International Diabetes Federation, National Heart, Lung and Blood Institute, American Heart Association, World Health Federation, International Atherosclerosis Society, and International Association of the Study of Obesity criteria.&#x0D; &#x0D; Results: Prevalence of Metabolic Syndrome (MetS) was 29.4% in 126 cases of Androgenetic Alopecia. The P Value was &lt;0.001 for obesity (52.4%), hypertension (35.7%), low HDL cholesterol (21.4%), hypertriglyceridemia (13.5%) and high fasting glucose (12.7%) respectively. Patients with higher severity grade of AGA had significantly higher prevalence of MetS and its components.&#x0D; &#x0D; Conclusions: Metabolic Syndrome showed a positive relation with Androgenetic Alopecia. Early screening for Metabolic Syndrome is beneficial in patients with androgenic alopecia to prevent them from developing coronary artery disease.

Editorial introductions.

Current Opinion in Lipidology was launched in 1990. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of lipidology is divided into six sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editor for this issue. SECTION EDITOR Erik StroesErik StroesErik S. G. Stroes is Chair of the Department of Vascular Medicine at the Academic Medical Center, Amsterdam, The Netherlands. After gaining his Doctor of Medicine degree from Erasmus University, Rotterdam, The Netherlands, he then specialized in internal medicine at University Medical Center, Utrecht, The Netherlands, and later in vascular medicine at the Academic Medical Center, Amsterdam. Professor Stroes’ research interests include the role of the vessel wall in atherosclerosis development and lipid disorders in relation to atherogenesis. He has been an investigator in numerous lipid-lowering trials using various surrogate markers, such as intima-media thickness and flow-mediated dilation, and more recently 3T magnetic resonance imaging as a surrogate marker for vascular disease progression. He has also been involved in the development of novel therapeutic moieties for dyslipidemia, such as lipoprotein lipase gene therapy, antisense oligonucleotide inhibition of apolipoprotein B synthesis, and reconstituted high-density lipoprotein infusion. He has been the recipient of numerous research grants and several awards. Professor Stroes is Chair of the Dutch Atherosclerosis Society, member of the Vascular Biology Working Group, member of the American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology, and former Chair of the Dutch Internist Vascular Society. He has published more than 300 papers in various peer-reviewed journals and authored several book chapters in the field. Gerald F WattsGerald F WattsGerald F Watts (DSc DM PhD FRCP FRACP) trained at Imperial College (St Mary's Hospital) and King's College (St Thomas’ Hospital) in the University of London. He is a consultant physician, specializing in lipid disorders and cardiovascular medicine, within the department of cardiology at Royal Perth Hospital, as well as Winthrop Professor of Cardiometabolic Medicine in the University of Western Australia. He is Chair of The Familial Hypercholesterolaemia (FH)-Australasia Network and executive board member of the International Atherosclerosis Society. His research interests include lipid disorders and cardiovascular prevention, with clinical interest focusing on delivering improved health care for patients and families with FH. Professor Watts is actively involved in undergraduate medical education and supervisors PhD students and post-doctoral fellows. He has authored over 500 published works, including scientific articles, reviews, book chapters and monographs, and is associate editor of Atherosclerosis, Journal Clinical Lipidology and Metabolism.

The effect of achieving LDL-C &amp;lt;1.8 mmol/L to prevent the first atherosclerotic cardiovascular events in the primary prevention settings of severe heterozygous familial hypercholesterolemia

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia” (FH) as a phenotype with the highest cardiovascular risk. LDL-C &amp;lt;2.5 mmol/l is a recommended therapeutic goal for the primary prevention settings of severe FH. However, given that ESC guidelines recommends LDL-C &amp;lt;1.8 mmol/l in FH patients, this stricter goal may be better to prevent the first atherosclerotic cardiovascular disease (ASCVD) in severe FH patients. Purpose To determine whether achieving LDL-C&amp;lt;1.8 mg/dl is more beneficial to reduce the first ASCVD events. Methods A total of 148 severe FH subjects without any history of ASCVD were analyzed. Severe FH was defined as untreated LDL-C &amp;gt;10.3 mmol/l, LDL-C &amp;gt;8.0 mmol/l+ 1 high-risk feature, LDL-C &amp;gt;4.9 mmol/l + 2 high-risk features according to IAS proposed statement. The occurrence of ASCVD (all-cause death, CAD, ischemic stroke and lower extremity artery disease (LEAD)) were compared in those with on-treatment LDL-C &amp;lt; and ≥1.8 mmol/L. Results 10.1% (=15/148) of study subjects achieved on-treatment LDL-C &amp;lt;1.8 mmol/l. They were more likely to receive PCSK9 inhibitor (15.0 vs. 66.7%, p&amp;lt;0.01), whereas there was no significant difference in FH-related physical characteristics (tendon xanthomas: 72.2 vs. 93.3%, p=0.12) and causative genotypes (LDLR: 68.4 vs. 66.7%, p=1.00, PCSK9: 8.3 vs. 6.7%, p=1.00, LDLR/PCSK9: 3.8 vs. 6.7%, p=0.48), untreated LDL-C (7.3±1.7 vs. 7.9±1.8 mmol/l, p=0.22) and lipoprotein(a) (23 [11–42] vs. 25 [15–70] mg/dl, p=0.41) levels between two groups. During the observational period (median=7.0 years), severe FH achieving on-treatment LDL-C &amp;lt;1.8 mmol/l was associated with a lower likelihood of experiencing ASCVD events (Figure 1). Of note, any cardiovascular events did not occur in severe FH who achieved on-treatment LDL-C &amp;lt;1.8 mmol/l. In those with on-treatment LDL ≥1.8 mmol/L, CAD (76.5%=26/34) was more dominant component of ASCVD, followed by ischemic stroke (17.6%=6/34) and LEAD (5.9%=2/34). Conclusions A significantly lower frequency of ASCVD was observed in severe FH who achieved LDL-C &amp;lt;1.8 mmol/L in the primary prevention settings. Given that only 10.1% of severe FH patients achieved LDL-C &amp;lt;1.8 mmol/l, more actions are required to motivate physicians for further intensified management of LDL-C in severe FH patients in the primary prevention settings. Funding Acknowledgement Type of funding sources: None.

How Can We Identify Very High-Risk Heterozygous Familial Hypercholesterolemia?

Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder that elevates low-density lipoprotein cholesterol and increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). However, despite their atherogenic lipid profiles, the cardiovascular risk of HeFH varies in each individual. Their variety of phenotypic features suggests the need for better risk stratification to optimize their therapeutic management. The current review summarizes three potential approaches, including (1) definition of familial hypercholesterolemia (FH)-related risk scores, (2) genetic analysis, and (3) biomarkers. The International Atherosclerosis Society has recently proposed a definition of severe FH to identify very high-risk HeFH subjects according to their clinical characteristics. Furthermore, published studies have shown the association of FH-related genetic phenotypes with ASCVD, which indicates the genetic analysis’s potential to evaluate individual cardiovascular risks. Biomarkers reflecting disease activity have been considered to predict the formation of atherosclerosis and the occurrence of ASCVD in HeFH subjects. Incorporating these risk stratifications will be expected to allocate adequate intensity of lipid-lowering therapies in HeFH subjects, which ultimately improves cardiovascular outcomes.

Latin American Consensus on management of residual cardiometabolic risk. A consensus paper prepared by the Latin American Academy for the Study of Lipids and Cardiometabolic Risk (ALALIP) endorsed by the Inter-American Society of Cardiology (IASC), the International Atherosclerosis Society (IAS), and the Pan-American College of Endothelium (PACE).

Background:Hypertension, hyperglycemia, dyslipidemia, overweight, obesity, and tobacco (smoking, chewing, and vaping), together with a pro-inflammatory and procoagulant state, are the main risk factors related to atherosclerotic cardiovascular disease.Objective and methods:A group of experts from the Americas, based on their clinical expertise in cardiology, cardiovascular prevention, and cardiometabolic (CM) diseases, joined together to develop these practical recommendations for the optimal evaluation and treatment of residual CM risk factors in Latin America, using a modified Delphi methodology (details in electronic TSI) to generate a comprehensive CM risk reduction guideline, and through personalized medicine and patient-centered decision, considering the cost-benefit ratio The process was well defined to avoid conflicts of interest that could bias the discussion and recommendations.Results:Residual risk reduction should consider therapeutic options adapted to specific patient needs, based on five treatment objectives: triglyceride-rich lipoproteins, inflammation, impaired glucose metabolism, high blood pressure, and prothrombotic status. Comprehensive control of all CM risk factors should be a priority to deal with this important public health problem and prevent premature deaths. The recommendations in this paper address the evidence-based treatment of CM risk and are intended for clinical application in Latin American countries.

Substantially Elevated Atherosclerotic Risks in Japanese Severe Familial Hypercholesterolemia Defined by the International Atherosclerosis Society.

The International Atherosclerosis Society (IAS) has proposed "severe familial hypercholesterolemia" (FH) as a phenotype with the highest cardiovascular risk. However, whether this criteria could appropriately stratify a high-risk Japanese patient with FH remains unknown. This study sought to characterize atherosclerotic cardiovascular diseases in IAS-defined Japanese subjects with severe FH. This study analyzed 380 clinically diagnosed subjects with heterozygous FH without any history of atherosclerotic cardiovascular diseases. Severe FH was defined as untreated low-density lipoprotein cholesterol >400mg/dL, >310mg/dL plus 1 high-risk feature, or >190mg/dL plus 2 high-risk features according to IAS-proposed statement. The occurrence of first and subsequent composite outcomes (cardiac [cardiac death + coronary artery disease + coronary revascularization] and noncardiac events [stroke + peripheral artery disease] was compared between subjects with severe (n=135) and non-severe (n=227) FH. Severe FH was identified in 40.3% of study population. They had higher low-density lipoprotein cholesterol (P< 0.001) and lipoprotein(a) (P = 0.03) levels. Moreover, they more frequently received high-intensity statin (P< 0.001), PCSK9 inhibitor (P< 0.001), and lipoprotein apheresis (P = 0.01) than nonsevere FH subjects did, which resulted in a lower on-treatment low-density lipoprotein cholesterol level of subjects with severe FH (113 ± 47.2 vs 130 ± 53.9mg/dL; P = 0.007). However, during the 7.4-year observational period, subjects with severe FH exhibited a 9.3-, 15.4-, and 5.9-fold greater risk for first composite (P< 0.001), cardiac (P< 0.001), and noncardiac outcomes (P = 0.02), respectively. Multivariate Cox proportional hazard model consistently revealed the 7.8- and 7.9-fold elevated risks of first (P< 0.001) and of subsequent (P< 0.001) composite outcomes in subjects with severe FH. Japanese subjects with severe FH present profound risks of both first and subsequent atherosclerotic cardiovascular diseases in the primary prevention settings. These findings support the clinical applicability of IAS-defined severe FH in Japanese patients, which identifies those who require further stringent antiatherosclerotic management.

Editorial introductions

Current Opinion in Lipidology was launched in 1990. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of lipidology is divided into six sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Erik S.G. StroesErik S.G. StroesErik S.G. Stroes is Chair of the Department of Vascular Medicine at the Academic Medical Center, Amsterdam, The Netherlands. After gaining his Doctor of Medicine degree from Erasmus University, Rotterdam, The Netherlands, he then specialized in internal medicine at University Medical Center, Utrecht, The Netherlands, and later in vascular medicine at the Academic Medical Center, Amsterdam. Professor Stroes’ research interests include the role of the vessel wall in atherosclerosis development and lipid disorders in relation to atherogenesis. He has been an investigator in numerous lipid-lowering trials using various surrogate markers, such as intima-media thickness and flow-mediated dilation, and more recently 3T magnetic resonance imaging as a surrogate marker for vascular disease progression. He has also been involved in the development of novel therapeutic moieties for dyslipidemia, such as lipoprotein lipase gene therapy, antisense oligonucleotide inhibition of apolipoprotein B synthesis, and reconstituted high-density lipoprotein infusion. He has been the recipient of numerous research grants and several awards. Professor Stroes is Chair of the Dutch Atherosclerosis Society, member of the Vascular Biology Working Group, member of the American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology, and former Chair of the Dutch Internist Vascular Society. He has published more than 300 papers in various peer-reviewed journals and authored several book chapters in the field. Gerald F. WattsGerald F. WattsGerald F. Watts (DSc DM PhD FRCP FRACP) trained at Imperial College (St Mary's Hospital) and King's College (St Thomas’ Hospital) in the University of London. He is a consultant physician, specializing in lipid disorders and cardiovascular medicine, within the department of cardiology at Royal Perth Hospital, as well as Winthrop Professor of Cardiometabolic Medicine in the University of Western Australia. He is Chair of The Familial Hypercholesterolaemia (FH)-Australasia Network and executive board member of the International Atherosclerosis Society. His research interests include lipid disorders and cardiovascular prevention, with clinical interest focusing on delivering improved health care for patients and families with FH. Professor Watts is actively involved in undergraduate medical education and supervisors PhD students and post-doctoral fellows. He has authored over 500 published works, including scientific articles, reviews, book chapters and monographs, and is associate editor of Atherosclerosis, Journal Clinical Lipidology and Metabolism.

HYPERURICEMIA AS A MARKER OF LIPID PEROXIDATION INTENSITY IN A POPULATION

The prevalence of hyperuricemia in the world has been steadily increasing over the past decade. According to various authors, the frequency of asymptomatic hyperuricemia in the population ranges from 5 to 35.1 per cent. The study of the relationship between purine metabolism disorders and the state of lipid peroxidation is still relevant due to numerous reports on the relationship between the processes of urate formation and free radical oxidation. Therefore, the aim of the study was to find out the value of hyperuricemia as a marker of the intensity of lipid peroxidation in a random population sample. Materials and methods. The group of participants was formed according to generally accepted epidemiological approaches using a random sample of workers and employees of an industrial enterprise (n=727 people, 457 men and 270 women, age ranged from 18 to 65 years, the average age was 38.13±5.10 years. Metabolic syndrome was diagnosed according to the recommendations of International Diabetes Federation, National Heart, Lung and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, and International Association for the Study of Obesity. Glucose homeostasis was evaluated according to the recommendations of the research society for the study of diabetes in India, Endocrine Society of India, 2020. Venous blood samples were taken on an empty stomach. We assessed the immunoreactive insulin content by immunochemiluminescent method, the concentration of triglycerides, cholesterol, high density lipoprotein by enzyme colorimetric method, xanthine and hypoxanthine were assessed by the method of S. V. Oreshnikov et al., uric acid was evaluated by colorimetric method, acylhydrazines – by the method of V. B. Gavrilov and M. I. Mishkorudny, malonic dialdehyde was assessed by the method of I. D. Steel, Garishvili T. G. in modification of L. I. Andreeva et al.; the level of total reduced SH groups was evaluated by the Elman photometric method, xanthine oxidase activity was studied by the photometric method, superoxide dismutase was examined by the T. V. Sirota method, and catalase in plasma and red blood cells – by the H. Aebi method. Results and discussion.&#x0D; Hyperuricemia was diagnosed in 118 (16.2%) patients. Violation of glucose homeostasis was diagnosed in 76 patients (10.5%): type 2 diabetes was found in 22 (3.03%) patients, glucose tolerance disorders were found in 47 (6.5%) patients, fasting hyperglycemia – in 7 (0, 96%), respectively. In a random population sample with hyperuricemia, the concentration of intermediate and final products of lipid peroxidation in the blood is significantly higher than in individuals with normouricemia. The concentration of reducing equivalents in the form of free SH groups does not significantly depend on the intensity of purine catabolism. The maximum intensity of lipid peroxidation is observed in the representatives of a random population sample with hyperuricemia in the presence of impaired glucose homeostasis. For this combination of pathological conditions, the concentrations of intermediate and final products of lipid peroxidation are significantly higher than for hyperuricemia by itself and hyperuricemia in combination with other components of the metabolic syndrome. The established links between disorders of purine metabolism and activation of lipid peroxidation demonstrate a close integration of purine metabolism pathology into hormonal and metabolic disorders of diabetogenic and atherogenic orientation at the level of a random population sample.

Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre.

Severe familial hypercholesterolemia (FH) individuals, refractory to conventional lipidlowering medications are at exceptionally high risk of cardiovascular events. The established therapeutic option of last choice is lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical usefulness of LA in a highly selected group of severe heterozygous FH (HeFH), as recently described by the International Atherosclerosis Society (IAS), for their efficacy in lipid reduction and safety. Efficacy and safety of LA were investigated in 318 sessions of 7 severe HeFH females with cardiovascular disease, over a mean period of 26.9 ± 6.5 months. Relative reduction of low density lipoprotein cholesterol (LDL-C) ≥ 60%, clinical complications and vascular access problems were evaluated and compared between the direct adsorption of lipoproteins (DALI) and lipoprotein filtration (Membrane Filtration Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a) [Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fibrinogen concentrations were investigated. The relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 ± 12.9%, 59.7 ± 9.1, 51.5 ± ± 14.2% and 71.3 ± 14.4%, respectively. A similar efficacy was found in both systems in LDL-C removal. DALI system led to larger depletions of Lp(a) (80.0 [76-83]% vs. 73.0 [64.7-78.8]%; p < 0.001). The frequency of clinical side effects and vascular access problems were low (8.5%). Long-term LA in severe HeFH individuals is safe and efficiently reduces LDL-C and Lp(a). Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the need for individualized application of the LA system in severe HeFH individuals.

Prevalence of cardiovascular risk factors in the Tunisian population: The ATERA-survey

Cardiovascular disease is the leading cause of death in Tunisia and worldwide. The incidence of cardiovascular diseases is directly proportional to that of the main atherosclerotic risk factors: arterial hypertension, diabetes mellitus, dyslipidemia, smoking and obesity. Up to day, in Tunisia there were no representative data on the adult prevalence rate. This is the reason behind starting a representative epidemiologic study to evaluate them and their evolution over time. Therefore the ATERA-Survey was initiated. Between January 2016 and February 2019, the Tunisian Association on Study and Research on Atherosclerosis (ATERA) and the International Atherosclerosis Society (IAS) made, for the first time, a large national study, the ATERA-Survey. It is a cross-sectional, descriptive and analytical study of Tunisians aged 25 to 75 years living in the 24 governorates of Tunisia. A systematic and stratified random survey was conducted. Using a complex methodology and an innovative way of conducting a field survey, by the means of a medical caravan. Each subject answered the questionnaire on the nutritional state and cardiovascular risk factors, underwent a physical examination and had a blood sample drawn. The survey involved 11,955 individuals. The average age was 55 years. The prevalence of risk factors was: hypertension (50.5%), diabetes (18.2%), dyslipidemia (44%), obesity (body mass index ≥ 30 kgm 2 ) (31.4%) and smoking (24.4%). This survey found a high prevalence of cardiovascular risk factors in a general population in Tunisia. This should lead to better develop a strategy to prevent cardiovascular diseases.

P938Extensive formation of atherosclerotic cardiovascular disease in subjects with severe familial hypercholesterolemia defined by the international atherosclerosis society criteria

Abstract Introduction The International Atherosclerosis Society (IAS) has proposed “severe familial hypercholesterolemia (FH)” as a FH phenotype with the highest cardiovascular risk. Coronary artery disease (CAD) represents a major atherosclerotic change in FH patients. Given their higher LDL-C level and atherogenic clinical features, more extensive formation of atherosclerosis cardiovascular disease including not only CAD but stroke/peripheral artery disease (PAD) may more frequently occur in severe FH. Methods 481 clinically-diagnosed heterozygous FH subjects were analyzed. Severe FH was defined as untreated LDL-C&gt;10.3 mmol/l, LDL-C&gt;8.0 mmol/l+ 1 high-risk feature, LDL-C&gt;4.9 mmol/l + 2 high-risk features or presence of clinical ASCVD according to IAS proposed statement. Cardiac (cardiac death and ACS) and non-cardiac (stroke and peripheral artery disease) events were compared in severe and non-severe FH subjects. Results Severe FH was identified in 50.1% of study subjects. They exhibit increased levels of LDL-C and Lipoprotein (a) with a higher frequency of LDLR mutation. Furthermore, a proportion of %LDL-C reduction&gt;50% was greater in severe FH under more lipid-lowering therapy (Table). However, during the observational period (median=6.3 years), severe FH was associated with a 5.9-fold (95% CI, 2.05–25.2; p=0.004) and 5.8-fold (95% CI, 2.02–24.7; p=0.004) greater likelihood of experiencing cardiac-death/ACS and stroke/PAD, respectively (picture). Multivariate analysis demonstrated severe FH as an independent predictor of both cardiac-death/ACS (hazard ratio=3.39, 95% CI=1.12–14.7, p=0.02) and stroke/PAD (hazard ratio=3.38, 95% CI=1.16–14.3, p=0.02) events. Clinical characteristics of severe FH Non-severe FH Severe FH P-value Baseline LDL-C (mmol/l) 5.3±1.5 6.6±2.0 &lt;0.0001 Lp(a) (mg/dl) 15 [8–28] 21 [10–49] &lt;0.0001 LDLR mutation (%) 49.6% 58.9% 0.00398 On-treatment LDL-C (mmol) 133 [106–165] 135 [103–169] 0.9856 %LDL-C reduction&gt;50% 21.3% 49.8% &lt;0.0001 High-intensity statin (%) 13.3% 42.3% &lt;0.0001 PCSK9 inhibitor (%) 6.3% 21.2% &lt;0.0001 Clinical outcome Conclusions Severe FH subjects exhibit substantial atherosclerotic risks for coronary, carotid and peripheral arteries despite lipid lowering therapy. Our finding underscore the screening of systemic arteries and the adoption of further stringent lipid management in severe FH patients.

Frailty and the Metabolic Syndrome - Results of the Berlin Aging Study II (BASE-II).

Frailty and the metabolic Syndrome (MetS) are frequently found in old subjects and have been associated with increased risk of functional decline and dependency. Moreover, central characteristics of the MetS like inflammation, obesity and insulin resistance have been associated with the frailty syndrome. However, the relationship between MetS and frailty has not yet been studied in detail. Aim of the current analysis within the Berlin Aging Study II (BASE-II) was to explore associations between MetS and frailty taking important co-variables such as nutrition (total energy intake, dietary vitamin D intake), physical activity and vitamin D-status into account. Complete cross-sectional data of 1,486 old participants (50.2% women, 68.7 (65.8-71.3) years) of BASE-II were analyzed. MetS was defined following the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity in 2009. Frailty was defined according to the Fried criteria. Limitations in physical performance were assessed via questionnaire, muscle mass was measured using dual energy X-ray absorptiometry (DXA) and grip strength using a Smedley dynamometer. Adjusted regression models were calculated to assess the association between MetS and Frailty. MetS was prevalent in 37.6% of the study population and 31.9% were frail or prefrail according to the here calculated frailty index. In adjusted models the odds of being frail/prefrail were increased about 50% with presence of the MetS (OR1.5; 95% CI 1.2,1.9; p= 0.002). Moreover the odds of being prefrail/frail were significantly increased with low HDL-C (OR: 1.5 (95%CI: 1.0-2.3); p = 0.037); and elevated waist circumference (OR: 1.65 (95%CI: 1.1-2.3); p = 0.008). The current analysis supports an association between MetS and frailty. There are various metabolic, immune and endocrine alterations in MetS that also play a role in mechanisms underlying the frailty syndrome. To what extent cytokine alterations, inflammatory processes, vitamin D supply and hormonal changes in age and in special metabolic states as MetS influence the development of frailty should be subject of further research.