Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. OBJECTIVE: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). METHODS: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. RESULTS: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease, PAD), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. CONCLUSIONS: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. RESULTS: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). CONCLUSIONS: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

A Posteriori Dietary Patterns and Coronary Artery Disease in a Greek Case-Control Study.

INTRODUCTION: Diet is one of the most important modifiable risk factors associated with cardiovascular health (CH). Research identifying dietary patterns (DPs) through data-driven analysis and reporting associations between DPs and coronary artery disease (CAD) outcomes is rather limited. OBJECTIVE: The aim of the present report was to generate DPs through factor analysis (FA) and to examine their association with CAD risk. METHODS: Participants (n = 1017) consisted of cases diagnosed with CAD (n = 356) and controls (n = 661) drawn from the THISEAS study. Demographic, anthropometric and lifestyle data were collected. Dietary components were generated through FA. Logistic regression analysis was performed to estimate CAD relative risks. RESULTS: FA generated seven dietary components, explaining 53.5% of the total variation in intake. The Western-type DP showed a modest significant association with CAD risk, after controlling for confounders (OR = 1.20; 95% CI = 1.09-1.32, p < 0.001). The vegetarian-type DP was not significantly associated with the likelihood of CAD (OR = 0.95; 95% CI = 0.84-1.04, p = 0.259). DISCUSSION: The Western-type DP was positively associated with CAD risk and the odds were further increased after controlling for confounders. This finding is in concordance with previously reported positive associations between Western patterns and CAD risk. Limited data exist regarding a posteriori DPs and their effect on CAD risk.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolemia: an expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is well established since three decades, lowering serum LDL-C levels by more than 70% per session. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment targets and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Regional differences in physicians' behavior and factors influencing the intensity of PCSK9 inhibitor therapy with alirocumab: a subanalysis of the ODYSSEY APPRISE study.

Background: Despite better accessibility of the effective lipid-lowering therapies, only about 20% of patients at very high cardiovascular risk achieve the low-density lipoprotein cholesterol (LDL-C) goals. There is a large disparity between European countries with worse results observed for the Central and Eastern Europe (CEE) patients. One of the main reasons for this ineffectiveness is therapeutic inertia related to the limited access to appropriate therapy and suitable dosage intensity. Thus, we aimed to compare the differences in physicians' therapeutic decisions on alirocumab dose selection, and factors affecting these in CEE countries vs. other countries included in the ODYSSEY APPRISE study. Methods: ODYSSEY APPRISE was a prospective, single-arm, phase 3b open-label (≥12 weeks to ≤30 months) study with alirocumab. Patients received 75 or 150 mg of alirocumab every 2 weeks, with dose adjustment during the study based on physician's judgment. The CEE group in the study included Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia, which we compared with the other nine European countries (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Spain, and Switzerland) plus Canada. Results: A total of 921 patients on alirocumab were involved [modified intention-to-treat (mITT) analysis], including 114 (12.4%) subjects from CEE countries. Therapy in CEE vs. other countries was numerically more frequently started with lower alirocumab dose (75 mg) at the first visit (74.6 vs. 68%, p = 0.16). Since week 36, the higher dose was predominantly used in CEE patients (150 mg dose in 51.6% patients), which was maintained by the end of the study. Altogether, alirocumab dose was significantly more often increased by CEE physicians (54.1 vs. 39.9%, p = 0.013). Therefore, more patients achieved LDL-C goal at the end of the study (<55 mg/dl/1.4 mmol/L and 50% reduction of LDL-C: 32.5% vs. 28.8%). The only factor significantly influencing the decision on dose of alirocumab was LDL-C level for both countries' groups (CEE: 199.2 vs. 175.3 mg/dl; p = 0.019; other: 205.9 vs. 171.6 mg/dl; p < 0.001, for 150 and 75 mg of alirocumab, respectively) which was also confirmed in multivariable analysis (OR = 1.10; 95% CI: 1.07-1.13). Conclusions: Despite larger unmet needs and regional disparities in LDL-C targets achievement in CEE countries, more physicians in this region tend to use the higher dose of alirocumab, they are more prone to increase the dose, which is associated with a higher proportion of patients reaching LDL-C goals. The only factor that significantly influences decision whether to increase or decrease the dose of alirocumab is LDL-C level.

Robust Bioinformatics Approaches Result in the First Polygenic Risk Score for BMI in Greek Adults.

Quantifying the role of genetics via construction of polygenic risk scores (PRSs) is deemed a resourceful tool to enable and promote effective obesity prevention strategies. The present paper proposes a novel methodology for PRS extraction and presents the first PRS for body mass index (BMI) in a Greek population. A novel pipeline for PRS derivation was used to analyze genetic data from a unified database of three cohorts of Greek adults. The pipeline spans various steps of the process, from iterative dataset splitting to training and test partitions, calculation of summary statistics and PRS extraction, up to PRS aggregation and stabilization, achieving higher evaluation metrics. Using data from 2185 participants, implementation of the pipeline enabled consecutive repetitions in splitting training and testing samples and resulted in a 343-single nucleotide polymorphism PRS yielding an R2 = 0.3241 (beta = 1.011, p-value = 4 × 10-193) for BMI. PRS-included variants displayed a variety of associations with known traits (i.e., blood cell count, gut microbiome, lifestyle parameters). The proposed methodology led to creation of the first-ever PRS for BMI in Greek adults and aims at promoting a facilitating approach to reliable PRS development and integration in healthcare practice.

Cardiovascular Magnetic Resonance Imaging Patterns in Rare Cardiovascular Diseases.

Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs' classification includes Class I-systemic circulation, Class II-pulmonary circulation, Class III-cardiomyopathies, Class IV-congenital cardiovascular diseases (CVD), Class V-cardiac tumors and CVD in malignancy, Class VI-cardiac arrhythmogenic disorders, Class VII-CVD in pregnancy, Class VIII-unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson-Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices.

Cardiovascular adaptations and inflammation in marathon runners.

Long-distance running has become increasingly popular. Cardiovascular adaptations to exercise are relevant to the specific sports and this is also the case in long-distance running. Significant changes regarding inflammatory and endothelial markers along with indices of oxidative stress are observed in marathon and ultra-marathon runners. However, data linking inflammatory marker levels with cardiovascular adaptations to marathon running are limited. The aim of the present study was to describe the cardiovascular adaptations observed in a group of ultra-marathon runners and the association with a series of inflammatory and endothelial markers measured in their plasma. A total of 43 ultra-marathon runners were assessed by echocardiography and a treadmill exercise test. Blood samples were used for tumor necrosis factor-α (TNF-α), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, IL-10, C-reactive protein, creatine phosphokinase (CPK) and oxidative stress indice measurements. Ultra-marathon runners who presented augmented left ventricular (LV) end diastolic diameters >55 mm had higher ADMA values (1.07±0.07 vs. 0.99±0.08 µmol/ml, P<0.01) and lower CPK values (192.5±21.3 vs. 219.1±37.3 mg/dl, P<0.05) compared with those with normal LV diameters. Runners with a moderate and severe abnormal indexed LV mass >131 g/m2 had statistically significant higher TNF-α values compared with runners, with mildly elevated and a normal LV mass indexed (16.2±1.42 vs. 14.0+1.16 pg/ml, P<0.05). Runners with an abnormal left atrial volume index (LAVI; >29 ml/m2) had higher IL-6 values compared with runners with a normal LAVI (1.09+0.19 vs. 0.99±0.08 pg/ml, P<0.05). ROC curves analysis revealed that ADMA values were able to predict an abnormal LV diameter detected by echocardiography [P<0.05; area under the curve (AUC), 0.763], while TNF-α values could predict an abnormal LV mass in marathon runners (P<0.05; AUC, 0.78). On the whole, the present study demonstrates that, in ultra-marathon runners, cardiovascular adaptations to running are characterized by a specific pattern of changes in inflammatory and endothelial markers, which in turn can be used to predict the occurrence of the observed adaptations.

Pathophysiology of cognitive dysfunction and the role of combined brain/heart magnetic resonance imaging (Review).

Normal cognitive function depends on a continuous and optimally regulated blood supply, and any pathology that further reduces cerebral blood perfusion in addition to that caused by aging could damage or destroy vulnerable neurons of the brain. Furthermore, glucose serves a crucial role as the primary fuel source for the mammalian brain and any disturbance in its circulating concentrations could directly affect brain function. The term cognitive dysfunction (CD), known also as 'brain fog', refers to deficits in attention, verbal and non-verbal learning, short-term and working memory, visual and auditory processing, mathematic problem solving, processing speed, focusing on a specific topic, and motor functioning. CD is the end-point of various cardiovascular, neural, metabolic and immune function impairments. Although CD has a serious impact on patient survival and quality of life, usually it is clinically underestimated. CD is currently assessed using cognitive tests (questionnaires), which have important limitations in their diagnostic capacity, specifically in the preclinical forms of CD. Cognitive tests may not identify subclinical cases of CD but diagnose CD only when symptoms are clinically overt. Furthermore, these tests do not provide information regarding the underlying pathophysiologic background of CD. The aim of the present review is to summarize the existing literature on CD and emphasize the role of combined brain-heart magnetic resonance imaging (MRI) in its early diagnosis, before CD questionnaires are abnormal. Combined brain/heart MRI has the potential to identify patients with CD at an early stage, facilitating risk stratification and early intervention. Furthermore, in parallel with brain assessment, it provides valuable information regarding the effect of the underlying disease on the myocardium. Equipment availability, physician familiarity and cost/effectiveness should be considered before wide clinical application of combined brain/heart MRI is recommended.

The Emerging Role of Combined Brain/Heart Magnetic Resonance Imaging for the Evaluation of Brain/Heart Interaction in Heart Failure.

Heart failure (HF) patients frequently develop brain deficits that lead to cognitive dysfunction (CD), which may ultimately also affect survival. There is an important interaction between brain and heart that becomes crucial for survival in patients with HF. Our aim was to review the brain/heart interactions in HF and discuss the emerging role of combined brain/heart magnetic resonance imaging (MRI) evaluation. A scoping review of published literature was conducted in the PubMed EMBASE (OVID), Web of Science, Scopus and PsycInfo databases. Keywords for searches included heart failure, brain lesion, brain, cognitive, cognitive dysfunction, magnetic resonance imaging cardiovascular magnetic resonance imaging electroencephalogram, positron emission tomography and echocardiography. CD testing, the most commonly used diagnostic approach, can identify neither subclinical cases nor the pathophysiologic background of CD. A combined brain/heart MRI has the capability of diagnosing brain/heart lesions at an early stage and potentially facilitates treatment. Additionally, valuable information about edema, fibrosis and cardiac remodeling, provided with the use of cardiovascular magnetic resonance, can improve HF risk stratification and treatment modification. However, availability, familiarity with this modality and cost should be taken under consideration before final conclusions can be drawn. Abnormal CD testing in HF patients is a strong motivating factor for applying a combined brain/heart MRI to identify early brain/heart lesions and modify risk stratification accordingly.

Moderately elevated lipoprotein (a) levels are associated with an earlier need for percutaneous coronary intervention in recurrent cardiovascular disease.

A significant number of cardiovascular disease (CVD) patients, with the target lipid levels, as set by the guidelines, achieved, continue to remain at risk. In this setting, lipoprotein (Lp) a role in CVD prognosis is regaining interest. Although Lp(a) is related to the arteriosclerotic process, there is not currently an adequate amount of data for the inclusion of Lp(a) levels as a primary therapeutic target in the treatment of coronary artery disease (CAD) patients. In this framework, the current retrospective study aims to investigate the association of Lp(a) levels with the adverse cardiovascular (CV) events presented in a 10 year follow-up of CVD patients with dyslipidemia and its association with the major CV risk factors. A statistically significant reduction in Lp(a) levels was observed during the follow-up period (72.8±45.6 vs. 68.3±41.8 mg/dl; McNemar test; P<0.001). The vast majority of patients who suffered a new acute myocardial infarction during the follow up period had Lp(a) levels >30 mg/dl (24/28 patients, mean ± standard deviation Lp(a), 83.1±36.6 mg/dl, P=0.001). Kaplan-Meier survival analysis did not find statistically significant differences in a percutaneous coronary intervention (PCI) time occurrence during the follow-up period between patients with low (≤30 mg/dl) and high (>30 mg/dl) Lp(a) levels (log-rank P=0.305). On the other hand, when a second and third PCI conducted during the monitoring period were included in the Kaplan Meier analysis as events, the mean time for a PCI was significantly shorter (7.2%; P=0.01) for patients with Lp(a) levels >30 mg/dl. In conclusion, the current study reported that patients with high Lp(a) values are more prone to the occurrence of new myocardial infarction, while the Lp(a) cut-off value of 30 mg/dl was linked in CVD patients to an earlier need for PCI, especially in the most vulnerable group of patients with more than one (recurrent) revascularizations.

Effect of Moderate Wine Consumption on Oxidative Stress Markers in Coronary Heart Disease Patients.

Evidence from research studies reports that wine consumption is associated with lower cardiovascular disease risk, partly through the amelioration of oxidative stress. The aim of the present study was to examine the effect of regular light to moderate wine consumption from coronary heart disease (CHD) patients compared to the effect induced by alcohol intake without the presence of wine microconstituents, on oxidation-induced macromolecular damage as well as on endogenous antioxidant enzyme activity. A randomized, single-blind, controlled, three-arm parallel intervention was carried out, in which 64 CHD patients were allocated to three intervention groups. Group A consumed no alcohol, and Group B (wine) and Group C (ethanol) consumed 27 g of alcohol/day for 8 weeks. Blood and urine samples were collected at baseline and at 4 and 8 weeks. Urine oxidized guanine species levels, protein carbonyls, thiobarbituric acid substances (TBARS) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were measured. Oxidized guanine species and protein carbonyl levels were significantly increased in the ethanol group during the intervention and were significantly decreased in the wine group. These results support the idea that wine's bioactive compounds may exert antioxidant actions that counteract the macromolecular oxidative damage induced by alcohol in CHD patients.

Cardiovascular Magnetic Resonance Detects Inflammatory Cardiomyopathy in Symptomatic Patients with Inflammatory Joint Diseases and a Normal Routine Workup.

Background. Patients with inflammatory joint diseases (IJD) are more likely to develop cardiovascular disease compared with the general population. We hypothesized that cardiovascular magnetic resonance (CMR) could identify cardiac abnormalities in patients with IJD and atypical symptoms unexplained by routine clinical evaluation. Patients-Methods. A total of 51 consecutive patients with IJD (32 with rheumatoid arthritis, 10 with ankylosing spondylitis, and 9 with psoriatic arthritis) and normal clinical, electrocardiographic and echocardiographic workups, were referred for CMR evaluation due to atypical chest pain, shortness of breath, and/or palpitations. Their CMR findings were compared with those of 40 non-IJD controls who were referred for the same reason. All participants were examined using either a 1.5 T or 3.0 T CMR system. For T1/T2 mapping, comparisons were performed separately for each field strength. Results. Biventricular systolic function was similar between groups. In total, 25 (49%) patients with IJD vs. 0 (0%) controls had replacement-type myocardial fibrosis (p < 0.001). The T2 signal ratio, early/late gadolinium enhancement, and extracellular volume fraction were significantly higher in the IJD group. Native T1 mapping was significantly higher in patients with IJD independent of the MRI field strength (p < 0.001 for both). T2 mapping was significantly higher in patients with IJD compared with controls only in those examined using a 1.5 T MR system­52.0 (50.0, 55.0) vs. 37.0 (33.5, 39.5), p < 0.001. Conclusions. In patients with IJD and a mismatch between cardiac symptoms and routine non-invasive evaluation, CMR uniquely identified a significant proportion of patients with myocardial inflammation. A CMR examination should be considered in patients with IJD in similar clinical settings.

Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH.

AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. METHODS: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. RESULTS: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. CONCLUSIONS: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

Volanesorsen: A New Era in the Treatment of Severe Hypertriglyceridemia.

INTRODUCTION: Familial chylomicronemia syndrome (FCS) is a rare inherited disease, mainly due to lipoprotein lipase (LPL) gene mutations, leading to lipid abnormalities. Volanesorsen, a second-generation 2'-O-methoxyethyl (2'-MOE) chimeric antisense therapeutic oligonucleotide, can decrease plasma apolipoprotein C3 and triglycerides (TG) levels through LPL-independent pathways. The European Medicines Agency has approved volanesorsen as an adjunct to diet in adult FCS patients with an inadequate response to TG-lowering therapy. Areas covered: Available clinical data on volanesorsen efficacy and safety are presented. Furthermore, we discuss the yearly treatment with volanesorsen of a 21-year-old female FCS patient with LPL mutation. Volanesorsen was well-tolerated and decreased patient's TG levels (from >5000 mg/dL (56 mmol/L) to 350-500 mg/dL (4-5.6 mmol/L)) at 12 months. Lipoprotein apheresis (LA) was stopped and there were no episodes of pancreatitis or abdominal pain. Expert opinion: Severe hypertriglyceridemia can potentially be fatal. Until recently, there was no specific treatment for FCS, apart from hypotriglyceridemic diet, fibrates, omega-3 fatty acids, and LA sessions. Therefore, volanesorsen represents a promising therapeutic solution for these patients. The main side effect of volanesorsen therapy is thrombocytopenia, which should be monitored and treated accordingly. Increasing evidence will further elucidate the clinical implications of volanesorsen use in daily practice.

A Case Series Assessing the Effects of Lomitapide on Carotid Intima-Media Thickness in Adult Patients with Homozygous Familial Hypercholesterolaemia in a Real-World Setting.

INTRODUCTION: Homozygous familial hypercholesterolaemia (HoFH) is characterised by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and results from multiple mutations in genes affecting the LDL receptor pathway. Patients are at risk of premature atherosclerotic cardiovascular disease (ASCVD) and premature death. Lomitapide is a microsomal triglyceride transfer protein inhibitor developed to treat HoFH, but cardiovascular outcome data are lacking. METHODS: We evaluated detailed data from five HoFH patients and one patient with heterozygous FH (HeFH) and a very severe phenotype. We also analysed confirmatory data from a further 8 HoFH cases. In total, we analysed data from patients in seven global centres in six countries who were all treated with lomitapide with long-term follow-up. Carotid intima-media thickness (CIMT) imaging was recorded on an ad hoc basis to monitor ASCVD in HoFH. RESULTS: Lomitapide resulted in marked decreases in LDL-C of 56.8-93.9% [77.7-93.9% in the 6 initial cases (mean nadir 64.8 ± 30.1 mg/dL); 56.8-86.0% in the 8 confirmatory cases (mean nadir 131.4 ± 38.2 mg/dL)]. CIMT regressed in 50% of cases (mean follow-up 5.0 ± 3.1 years in initial six cases, and 4.4 ± 1.4 years in confirmatory cases). In the remaining patients, CIMT showed little further change. In patients where assessments of plaque area were available, regression or stabilisation in CIMT was accompanied by clinically significant regression of plaque area. CONCLUSIONS: Lomitapide reduces LDL-C levels in patients with HoFH and severe LDL-C phenotypes, and results in stabilisation and/or regression of CIMT, which is an established marker of ASCVD risk. Additional data are needed to determine if this confers a survival benefit in these very high-risk patients.