Familial Hypercholesterolemia Registry Research Articles

Ocular manifestations of severe familial hypercholesterolemia

BackgroundTo study ocular manifestations of patients with severe familial hypercholesterolemia (FH). MethodsIn this population-based case-control study, patients suffering from severe familial hypercholesterolemia from the Lebanese Familial Hypercholesterolemia Registry, along with age and gender-matched healthy controls were recruited. All participants underwent a comprehensive eye examination, and patients underwent fluorescein angiography as well. Logistic regression models were used to identify any association between patients with severe familial hypercholesterolemia and abnormal eye findings, while adjusting for hypertension and pack-year smoking. The main outcome measure of this study was the development of ocular vascular abnormalities. Results28 patients and 28 controls were recruited. Patients with severe familial hypercholesterolemia had significantly greater odds of developing corneal arcus and xanthelasmas than the control group (p < 0.001). Retinal vascular abnormalities (plaques) were exclusively and more significantly present in patients with familial hypercholesterolemia (18 %). Similarly, retinal arteriosclerosis was exclusively and significantly more prevalent in the familial hypercholesterolemia group (p < 0.001, adjusted odds ratio 6.8). Stratification by LDL levels and genotypes did not show any significant change in the prevalence of any ocular finding. ConclusionIn addition to the well-established increase in incidence of corneal arcus and xanthelasmas, severe familial hypercholesterolemia patients have more prevalent retinal vascular abnormalities that include vascular plaques and arteriosclerosis.

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

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. 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. Adult patients ( n = 2156, mean age 50 ± 15 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. 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.

Abstract 17207: Usefulness of Polygenic Risk Score for Intraventricular Septal Diameter in Patients With Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant monogenic disease characterized by thickened heart muscles, particularly at the intraventricular septum (IVS), and an increased risk of arrythmias and sudden death. Recently, in addition to monogenic screening, the polygenic risk score (PRS) has been proposed as a potentially useful tool for risk stratification in several cardiovascular diseases. However, it remains unclear whether PRS is also beneficial for risk stratification of patients with HCM. Methods: We recruited and genotyped HCM patients from the Kanazawa University Mendelian Disease (KUMD) HCM registry and controls from the KUMD non-HCM familial hypercholesterolemia registry. The PRS was calculated from over 3 million genotyped with imputed variants of each participant for IVS diameter (PRS IVS ) using a publicly available summary statistic at the National Bioscience Database Center. We assessed the PRS IVS distributions among the monogenic HCM, causal variant negative HCM, and control groups. We also tested the associations of PRS IVS with the IVS diameters within each group. Results: We evaluated a total of 400 participants (267 HCM patients, including 79 with monogenic HCM and 188 with causal variant negative HCM, and 133 controls) for the analyses. Compared to the controls, PRS IVS was significantly higher in both monogenic HCM (0.12923 in Monogenic HCM vs. 0.09057 in controls, age- and sex-adjusted p = 0.02) and causal variant negative HCM patients (0.11127 in causal variant negative HCM vs. 0.09057 in controls, p = 9.9x10 -4 ). However, no associations were found between PRS IVS and IVS diameters in any of the groups. Conclusions: In this study, both the monogenic HCM and causal variant negative HCM groups demonstrated significantly higher PRS IVS than non-HCM controls. However, we found no evidence to suggest that PRS IVS might be useful for risk stratification in patients with HCM.

Compliance of heterozygous familial hypercholesterolemia patients: 5-years follow-up of the Russian familial hypercholesterolemia registry

Compliance of heterozygous familial hypercholesterolemia patients: 5-years follow-up of the Russian familial hypercholesterolemia registry

The Association of Thyroid-Stimulating Hormone (TSH) Levels and Lipid Profile in Euthyroid Patients with Familial Hypercholesterolemia.

Previous studies reported a relationship between thyroid-stimulating hormone (TSH) and low-density lipoprotein cholesterol (LDL-C) levels. In this study, we aim to evaluate the impact of TSH levels on lipid profile in patients with familial hypercholesterolemia (FH) and euthyroid state. Patients were selected from the Isfahan FH registry. The Dutch Lipid Clinic Network (DLCN) criteria are used to detect FH. Patients were classified into no FH, possible FH, probable FH, and definite FH groups based on the DLCN scores. Patients with any cause of secondary hyperlipidemia, including hypothyroidism, were excluded from this study. The study group consisted of 103 patients with possible FH, 25 patients with definite FH, and 63 individuals with no FH. The mean TSH and LDL-C levels among participants were 2.10 ± 1.22 mU/l and 142.17 ± 62.56 mg/dl, respectively. No positive or negative correlation was found between serum TSH and total cholesterol (P value = 0.438), high-density lipoprotein cholesterol (P = 0.225), triglycerides (P value = 0.863), and LDL-C (P value = 0.203). We found no correlation between serum TSH levels and lipid profiles in euthyroid patients with FH.

Design, Rationale, and Preliminary Results of the Canadian Homozygous Familial Hypercholesterolemia Registry: 2008 to 2022 Update

&#x0D; Homozygous familial hypercholesterolemia (HoFH) is an orphan disease characterized by extreme elevations of low-density lipoprotein cholesterol (LDL-C) in the blood and premature atherosclerotic cardiovascular disease.&#x0D; Untreated, survival beyond 30 years is rare.&#x0D; The Canadian HoFH Registry was created by clinicians from across Canada to understand the burden of disease, current treatments, outcomes, and costs to society.&#x0D; The registry will be used to inform decisions for access to specialized therapies, such as LDL apheresis and orphan medications.&#x0D; To date, 79 cases of HoFH have been identified across the country, and 52 patients from 5 provinces have been enrolled.&#x0D;

Genetic testing for familial hypercholesterolemia in Quebec, Canada: a single-centre retrospective cohort study.

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease caused by elevated low-density lipoprotein cholesterol (LDL-C) levels. We determined the impact of a full next-generation sequencing (NGS) genetic panel on reclassification of patients with a clinical diagnosis of FH in Quebec compared to the partial genetic panel currently offered by the Quebec Ministère de la Santé et des Services sociaux (Ministry of Health and Social Services) (MSSS), which includes 11 variants that are common in French Canadians. We conducted a retrospective cohort study in a subgroup of patients in the Canadian FH Registry seen at the McGill University Health Centre Preventive Cardiology/Lipid Clinic, Montréal, between September 2017 and September 2021 who were clinically diagnosed with severe hypercholesterolemia, probable FH or definite FH according to the Canadian definition of FH. Next-generation sequencing of the LDLR, APOB and PCSK9 genes, and multiplex ligation-dependent probe amplification of the LDLR gene to detect genetic variants, were performed. Among 335 consecutive patients with heterozygous FH (184 men [54.9%] and 151 women [45.1%]), the baseline LDL-C level was 6.96 (standard deviation 1.79) mmol/L. Patients identified through cascade screening were 11 years younger on average than index patients, and smaller proportions presented to the clinic with cardiovascular risk factors. A pathogenic FH variant was identified in 169 (73.8%) of the 229 patients who underwent genetic testing; the majority had variants in the LDLR (146 [86.4%]) or APOB (24 [14.2%]) gene. The genetic panel offered by the MSSS accounted for only 48% of the variants identified with the full NGS panel. Of the 229 patients, 90 (39.3%, 95% confidence interval 32.9%-46.0%) were reclassified from a clinical diagnosis of probable FH to definite FH after genetic screening with a full FH panel. Genetic testing in patients suspected of having FH provided diagnostic certainty and permitted many patients with a clinical diagnosis of probable FH to be reclassified as having definite FH. Genetic screening allows for increased identification of patients with FH and may therefore help reduce the burden of cardiovascular disease and mortality rates among Canadians with FH. Trial registration: ClinicalTrials.gov, no. NCT02009345.

Primary Care Physicians' Perspectives on Identifying Familial Hypercholesterolaemia in Primary Care: A Qualitative Study.

Context Familial hypercholesterolaemia (FH) is a common autosomal dominant disorder, causing elevated cholesterol from birth, premature heart disease, and early death. Objective This study explored primary care physicians' experiences and perspectives on identifying FH in Malaysian primary care. Study Design and Analysis A qualitative study involving semi-structured interviews and focus group discussions with 22 primary care physicians (PCPs) in two primary care clinic settings. The interviews and focus group discussions were audio recorded, and the recordings were transcribed verbatim. The data in the transcripts were analysed using thematic approach. Setting Primary Care Clinics Population Studied Primary Care Physicians in two primary care clinics. Intervention A qualitative study involving semi-structured interviews and focus group discussions Outcome Measures Primary Care Physicians' perceptions and experiences of identifying individuals at high risk of FH in their clinical practice, and the acceptability and perceived challenges of trying to do this were explored during the interviews and focus group discussions. Findings PCPs felt there was potential for FH to be identified earlier in primary care. They had some existing knowledge and awareness of diagnostic criteria for FH but highlighted several challenges. In their practice, this included limited time in routine clinical care, availability of medication and clinical expertise; and critical lack of family history and physical examination findings in health records. The barriers on a systemic level were shortage of lipid specialist services and the absence of local care pathways for FH. The PCPs recommended a user-friendly case-finding tool for FH, and establishing FH registry and clinical practice guideline in Malaysia, alongside a national FH screening strategy and awareness campaigns for both clinicians and general public. Conclusions PCPs are positive about improving the identification of FH in primary care. However greater support in their practice and wider system developments and change are needed.

Prevalence of Diabetes and Its Association with Atherosclerotic Cardiovascular Disease Risk in Patients with Familial Hypercholesterolemia: An Analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

Familial hypercholesterolemia (FH) and type 2 diabetes mellitus (T2DM) are both associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Little is known about the prevalence of T2DM and its association with ASCVD risk in FH patients. This was a cross-sectional analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH) including adults with FH (n = 1719, mean age 51.3 ± 14.6 years). Of FH patients, 7.2% had a diagnosis of T2DM. The prevalence of ASCVD, coronary artery disease (CAD), and stroke was higher among subjects with T2DM compared with those without (55.3% vs. 23.3%, 48.8% vs. 20.7%, 8.3% vs. 2.7%, respectively, p &lt; 0.001). When adjusted for age, systolic blood pressure, smoking, body mass index, hypertension, waist circumference, triglyceride levels, high-density lipoprotein cholesterol levels, and gender, T2DM was significantly associated with prevalent ASCVD [OR 2.0 (95% CI 1.2-3.3), p = 0.004]. FH patients with T2DM were more likely to have undergone coronary revascularization than those without (14.2% vs. 4.5% for coronary artery bypass graft, and 23.9% vs. 11.5% for percutaneous coronary intervention, p &lt; 0.001). T2DM is associated with an increased risk for prevalent ASCVD in subjects with FH. This may have implications for risk stratification and treatment intensity in these patients.

A familial hypercholesterolemia registry as the main tool for adequate management of the disease.

To evaluate the experience of FH registry conducted in Karelia Republic. FH registry in Karelia is existing from 2004, it includes 350 patients with heterozygous FH (110 with definite FH), the mean age is 48 ± 2.3 years. The genetic study was performed in 102 patients (29.1%). The creation of the registry has contributed to the active identification of FH, and now the estimated frequency of FH occurrence in Karelia may be 1:300, in patients with cardiovascular disease 1:10. We also analyzed genetic features of FH in our republic and found that the LDL-C level, above which the probability of LDL receptor mutation increases in Karelia, is 6.5 mmol/L. We analyzed risk factors of ischemic heart disease and the prognosis in FH. The creation and maintenance of a registry is an effective way of organizing timely diagnosis and adequate treatment of FH patients.

SEX DISPARITIES IN TREATMENT AND CLINICAL OUTCOMES OF FAMILIAL HYPERCHOLESTEROLEMIA

SEX DISPARITIES IN TREATMENT AND CLINICAL OUTCOMES OF FAMILIAL HYPERCHOLESTEROLEMIA

Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: An analysis from the hellas-fh

Background and 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 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 CVD 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 HeFH. Background and 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 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 CVD 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 HeFH.

Detection of comorbidities in patients with familial hypercholesterolemia in the Ukrainian familial hypercholesterolemia registry

Detection of comorbidities in patients with familial hypercholesterolemia in the Ukrainian familial hypercholesterolemia registry

Identification of familial hypercholesterolaemia (FH) in Malta: An update of the FH registry and cascade screening programme in Malta

Background and Aims : FH is a common inherited condition causing premature cardiovascular disease; early identification and implementation of available, cost-effective, lipid-lowering therapy reduces risk significantly-yet FH is underdiagnosed and undertreated. Its autosomal dominant inheritance mandates family screening - ideally using genetic testing, which is constrained by availability, resources, and unknown mutation patterns in understudied populations. Under 10% of the predicted population is included in the Malta FH Register (c.

^Sex Disparities in the Treatment and Outcomes of Familial Hypercholesterolemia

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> Fonds de recherche du Québec - Santé (FRQ-S). <h3>Background/Synopsis</h3> Familial hypercholesterolemia (FH), an inherited condition equally prevalent in males and females, is characterized by elevated low-density lipoprotein cholesterol (LDL-C) in the blood. If left untreated, FH leads to the development of premature atherosclerotic cardiovascular disease (ASCVD) and death. Many barriers to care in FH exist, which can result in low rates of diagnosis and suboptimal treatment and outcomes. Sex disparities have been identified as an important barrier to care in CVD, however their influence on treatment and lipid target achievement in FH remains to be explored. <h3>Objective/Purpose</h3> To determine sex differences in treatment and lipid level achievement in Heterozygous (HeFH) patients at the MUHC. <h3>Methods</h3> Here we performed a longitudinal registry analysis of sex differences in treatment and lipid level achievement in HeFH patients at the MUHC. Patients were included in the study if they were diagnosed as either "definite", "probable", or "possible" FH based on the Simon- Broome criteria, Dutch Lipid Clinic Network criteria, or the new Canadian FH definition. Differences between males and females were calculated using a t-test or chi-squared test. <h3>Results</h3> There were 127 females and 162 males from the McGill FH Registry included in the analysis. The mean age at the initial clinic visit was 49±17 years for females and 45±16 years for males (p=0.04). At the most recent clinic visit, there were more males (89%) than females (76%) taking statins (p=0.7), and only 35% of females were on high-intensity statins, compared to 74% of males (p=0.002). Interestingly, statin intolerance was reported in 40% of females and 22% of males (p=0.02). We then examined guideline-recommended lipid target achievement between both sexes. At baseline, males and females had similar mean LDL-C levels of 6.9±2.2 mmol/L and 6.7±1.6 mmol/L respectively (p=0.7). Despite this, at the most recent visit, 55% of males reached a target LDL-C of 2.5 mmol/L compared to just 32% of females (p=0.02). As well, from baseline to most recent visit, females reduced their LDL-C by 51%, whereas males lowered their LDL-C by 62% (p=0.01). Thus, fewer females are reaching appropriate guideline-based target LDL-C levels compared to males. <h3>Conclusions</h3> Our analysis reveals a sex bias in FH patients in favor of males regarding treatment intensity and lipid level target achievement. Identifying these imbalances will allow us to break down these barriers in care through educational initiatives and additional training, to improve quality of life and life expectancy of individuals with FH.

Applying an LDL-C threshold-based approach to identify individuals with familial hypercholesterolemia

Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. The optimal electronic health record (EHR) screening strategy for FH is unclear. To evaluate an LDL-C threshold-based approach of identifying patients with FH from the EHR to determine the optimal LDL-C range for FH consideration. Individuals from UT Southwestern Medical Center with an LDL-C level ≥190mg/dL at any time were enrolled in an FH registry. These 5,786 patients were divided into four categories of LDL-C (190- 219, 220 - 249, 250 - 299, and ≥ 300mg/dL) with 100 individuals randomly selected for manual chart review in each category. Chart review included 1) the presence of secondary causes of dyslipidemia, 2) diagnosis of possible/definite FH by modified Simon Broome criteria, and 3) probable/definite FH by modified Dutch Lipid Clinic Network (DLCN) criteria. Of the 400 individuals with an LDL-C level ≥190mg/dL (mean age 52 years ± 14), the presence of secondary causes increased across each LDL-C category (p < 0.001) with the greatest prevalence in those ≥ 300mg/dL (52%). The prevalence of possible/probable or definite FH also varied by LDL-C category, with the highest prevalence of FH by Simon Broome criteria in the 220 - 249mg/dL category (52%) and by DLCN criteria in the 250 - 299mg/dL category (46%). Among those with LDL-C ≥ 190mg/dL, the prevalence of secondary causes increased markedly with higher LDL-C, while the diagnosis of FH has a parabolic relationship. Patients with intermediate LDL-C (220 - 299mg/dL) may be the optimal group to prioritize for FH screening.

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

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. 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. 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. Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

Elevated Lipoprotein(a) Level Influences Familial Hypercholesterolemia Diagnosis.

Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] level are the most common inherited disorders of lipid metabolism. This study evaluated the impact of high Lp(a) level on accuracy Dutch Lipid Clinic Network (DLCN) criteria of heterozygous FH diagnosis. A group of 206 individuals not receiving lipid-lowering medication with low-density lipoprotein cholesterol (LDL-C) >4.9 mmol/L was chosen from the Russian FH Registry. LDL-C corrected for Lp(a)-cholesterol was calculated as LDL-C − 0.3 × Lp(a). DLCN criteria were applied before and after adjusting LDL-C concentration. Of the 206 patients with potential FH, a total of 34 subjects (17%) were reclassified to less severe FH diagnosis, 13 subjects of them (6%) were reclassified to “unlike” FH. In accordance with Receiver Operating Characteristic curve, Lp(a) level ≥40 mg/dL was associated with FH re-diagnosing with sensitivity of 63% and specificity of 78% (area under curve = 0.7, 95% CI 0.7–0.8, p < 0.001). The reclassification was mainly observed in FH patients with Lp(a) level above 40 mg/dL, i.e., 33 (51%) with reclassified DLCN criteria points and 22 (34%) with reclassified diagnosis, compared with 21 (15%) and 15 (11%), respectively, in patients with Lp(a) level less than 40 mg/dL. Thus, LDL-C corrected for Lp(a)-cholesterol should be considered in all FH patients with Lp(a) level above 40 mg/dL for recalculating points in accordance with DLCN criteria.

Screening for Familial Hypercholesterolemia using Epic Secure Chat in Comparison to Epic Letter as Educational Outreach˄

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Familial hypercholesterolemia (FH) is an autosomal dominant disorder involved LDL-c uptake and metabolism. It occurs in 1:200-250 individuals. If untreated, FH confers an increased risk of ASCVD. In the USA, approximately 5% of all MIs are caused by FH. However only 1-10% of these cases have been identified. This underdiagnosis places an immense burden on individuals and the health care system. Atlantic Health System (AHS) is a clinical site for the national Cascade FH Registry, with the goal to identify patients and their families with FH. There are many barriers to screening including financial, social, and legal considerations. One of these barriers is the lack of general awareness to recognize FH among many primary care physicians (PCP)s. <h3>Objective/Purpose</h3> In this study we used our electronic medical record (EMR) EPIC Chat to screen for FH by contacting PCPs. In 2019, we contacted PCPs using Epic Letter and generated a 6% response rate. We predicted that using Epic Chat we would have a larger response. <h3>Methods</h3> Our EMR database consist of 1,004 clinicians including 195 PCPs and 404,595 unique patients. We identified approximately 1,000 patients with LDL >160 mg/dL and selected 200 patients with probable FH. We contacted their PCPs via Epic Chat by using the same IRB approved letter we used a year prior to send Epic Letters. <h3>Results</h3> Epic Chat generated a response of 28% (n=56) compared to our prior response rate of 6.5% (n=13) using Epic Letter. Most physicians responded immediately. They were interested and thankful to learn about our educational outreach. <h3>Conclusions</h3> Our outreach with Epic Chat generated a robust response compared to Epic Letter. Epic Chat is embedded in the Epic workflow, facilitating an immediate response and dialogue among users. Since our present study is two years later, it is possible that our screening program has become better known. However, it is unlikely to explain such a large difference in response. We believe this study shows by using EPIC Chat, screening programs designed to reach PCPs can be greatly improved.

Клініко-лабораторні та генетичні паралелі у хворих з гетеро- та гомозиготними сімейними гіперхолестеринеміями в Україні

The aim – clinical, laboratory and genetic parallels of patients with hetero- and homozygous familial hypercholesterolemia (FH) in Ukraine.Materials and methods. 231 FH patients were included in the Ukrainian FH Registry: 8 children (under 18 years of age) and 223 adult patients (197 heterozygous FH (HeFH) patients, 26 homozygous FH (HoFH) patients, verified according to DLCN criteria). The patients underwent general clinical, laboratory, instrumental examinations and genetic testing.Results and discussion. Among HeFH patients against the background of early manifestation of atherosclerosis, the male patients were more likely to have coronary heart disease and peripheral atherosclerosis, xanthomatosis and higher DLCN scores against an increase in % obesity and hypertension among HeFH women on the background of significantly lower DLCN. In the HoFH patients despite the inclusion of mostly reproductive aged females in the Registry, it is among women the most severe variants of FH were registered. They were characterized by a predominance of coronary heart disease, MI, xanthomatosis, the need for myocardial revascularization and prosthetic heart valves on the background of higher DLCN scores, cholesterol, LDL-C and ApoB values ​​up to 1.7±0.2 g/L and Lp (a) up to 119.5±31.4 nmol/L. In HoF patients and the most severe variants of the clinical course, who had levels of «statin naive» cholesterol and LDL above 20 mmol/L a more significant increase in these values were found: ApoB average 3.2±1.1 (maximum – 4.72) g/L and Lp (a) to 121.5±41.5 (maximum – 163) nmol/L and reduction of apoA1 level to 0.9±0.1 g/L.Conclusions. HeFH patients retain gender features of the risk factors profile, which corresponds to the main gender-related trends revealed by the Ukrainian population study with a predominance of coronary heart disease, peripheral atherosclerosis and xanthomatosis on the background of higher scores on DLCN in men. HoFH patients showed a reverse trend, namely among women – the predominance of coronary heart disease, myocardial infarction, xanthomatosis and the need for revascularization on the background of a higher score on DLCN. The cohort of HoFH women revealed the most severe FH cases with LDL-C &gt; 20 mmol/L, which was accompanied in 100 % of cases by early development of coronary heart disease and the need for myocardial revascularization, despite young age (36.5±3.9) and preserved reproductive function. According to HoFH patients genetic testing, pathogenetic mutations were detected in 72.3 % of women and 55.5 % of men (92.3 % in LDLR and 7.7 % in apoB). In the cohort of the most severe patients with LDL and LDL cholesterol &gt; 20 mmol/L, genetic mutations were detected in 100 %