Familial Hypercholesterolemia Registry Research Articles

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 %

SEX DISPARITIES IN THE TREATMENT AND OUTCOMES OF FAMILIAL HYPERCHOLESTEROLEMIA

<h3>BACKGROUND</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>METHODS AND RESULTS</h3> Here we performed a longitudinal registry analysis of sex differences in treatment and lipid level achievement in Heterozygous FH (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. 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). First, we analyzed sex differences in lipid lowering medication use. 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>CONCLUSION</h3> Our analysis reveals a sex bias in FH patients in favour of males in regard to 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.

Загальний аналіз клініко-лабораторних характеристик пацієнтів, які увійшли до Українського реєстру хворих із сімейною гіперхолестеринемією

The aim – to evaluate clinical and laboratory characteristics of patients of the Ukrainian familial hypercholesterolemia registry taking into account gender differences. Materials and methods. 231 patients with familial hypercholesterolemia were included to the Ukrainian Familial Hypercholesterolemia Registry: 8 children (under 18 years of age) and 223 adult patients (68 men (30.5 %), mean age 43.4±1.3 and 155 women) 69.5 %) – 45.5±1.0 years) with familial hypercholesterolemia verified according to the DLCN criteria. General clinical, laboratory, instrumental examinations and genetic testing were performed.Results and discussion. In the general registry among the patients with familial hypercholesterolemia in the setting of early manifestation of atherosclerosis the male patients with familial hypercholesterolemia were more likely to have coronary artery disease, premature coronary artery disease, cerebral and peripheral atherosclerosis, xanthoma, hypertriglyceridemia, diabetes mellitus, smoking and a history of MI, which caused a higher DLCN score (9.3 points in men against 7.8 points in women, p&lt;0.05). Female patients with familial hypercholesterolemia had a higher percentage of obesity and hypertension, which corresponds to the main gender trends of the Ukrainian population study.Conclusions. Since 2017, for the first time in Ukraine, the register of patients with familial hypercholesterolemia has been initiated. In December 2019 the most severe form – homozygous familial hypercholesterolemia – was first included in the list of orphan diseases by the Order of the Ministry of Health of Ukraine. According to the analysis of the data of the Ukrainian familial hypercholesterolemia registry, this pathology is diagnosed rather late and insufficiently in Ukraine. In patients with familial hypercholesterolemia, against the background of an earlier manifestation of atherosclerotic lesions, gender features of the cardiovascular risk factors profile, which are characteristic of the entire adult population of Ukraine, are preserved. The lower severity of familial hypercholesterolemia clinical manifestations in women according to the general Ukrainian familial hypercholesterolemia registry may be due to the predominance of heterozygous forms in the registry and inclusion of women of reproductive age against the background of preserved antiatherogenic effects of estrogen to the registry.

Phenotypic and Genetic Analyses of Korean Patients with Familial Hypercholesterolemia: Results from the KFH Registry 2020.

Aims: Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH. Methods: A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) ＞190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C ＞225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified. Results: Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L inLDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease. Conclusions: Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.

Sex differences in HoFH patients of the Ukrainian familial hypercholesterolemia registry

Background and Aims: Homozygous Familial hypercholesterolemia (HoFH)- is a rare genetic lipid disorder associated with increased LDL-C and premature atherosclerotic cardiovascular disease (ASCVD), but gender specificities are not sufficiently studied.

Familial Hypercholesterolemia (FH) in Iran: Findings from the Four-Year FH Registry.

Background Familial hypercholesterolemia (FH) is a common autosomal dominant disease. Its diagnosis in Iran was uncommon. Iran registry of FH (IRFH) has been started from 2017 from Isfahan. In this study, we report the four-year FH registry. Methods The Iran FH registry is an ongoing study which is followed by a dynamic cohort. It has been started from 2017. The patients are selected from laboratories due to high cholesterol level and who have history of premature cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) criteria are used for the detection of FH. Cascade screening is performed for detection of first-degree relative of patients. Results Among the 997 individuals included in this registry, they were 522 (mean age 51.41 ± 12.91 year), 141 (mean age 51.66 ± 8.3 year), and 129 (mean age 41 ± 16.5 year) patients from laboratories, premature cardiovascular disease, and relatives, respectively. In total, 263 patients were diagnosed with probable or definite FH, and others were in the possible group. Low-density lipoprotein cholesterol (LDL) level was 141.42 ± 45.27 mg/dl in the laboratory group and 54.9% of patients were on LLT treatment. In patients with premature cardiovascular disease and FH, the LDL level was 91.93 ± 32.58 and was on LLT treatment. The LDL concentration in the first relative of FH patients was 152.88 ± 70.77 and 45.7% of them are on LLT therapy. Conclusions Most of FH patients were underdiagnosed and undertreated before their inclusion in the IRFH. Cascade screening helps in the improvement of diagnosis.

Genetic Analysis in a Taiwanese Cohort of 750 Index Patients with Clinically Diagnosed Familial Hypercholesterolemia.

Aim: Familial hypercholesterolemia (FH) is underdiagnosed in most countries. The genetic heterogeneity of FH requires an algorithm to efficiently integrate genetic testing into clinical practice. We aimed to report the spectrum of genetic mutations from patients with clinically diagnosed FH in Taiwan. Methods: Patients with LDL-C＞190 mg/dL or those with probable or definite FH according to the Taiwan Lipid Guidelines underwent genetic testing. Samples from 750 index patients from the Taiwan FH registry were screened using custom-made mass spectrometry, followed by targeted next generation sequencing (NGS) and/or multiplex ligation-dependent probe amplification (MLPA) if found negative. Results: The mean age of the patients was 52.4±15.1 years and 40.9% were male. Mutations were detected in 445 patients (59.3%). The distribution of mutations was as follows:LDLR (n=395),APOB (n=58),PCSK9 (n=0), andABCG5 (n=3). The most common mutations wereAPOB c.10579 C＞T (p.R3527W) (12.6%),LDLR c.986 G＞A (p.C329Y) (11.5%), andLDLR c.1747 C＞T (p.H583Y) (10.8%).LDLR c.1187-10 G＞A (IVS 8-10) andAPOB c.10580 G＞A (p.R3527Q) were detected using targeted NGS in Taiwan for the first time. Four novel mutations were identified, includingLDLR c.1060＋2 T＞C (IVS 7＋2),LDLR c.1139 A＞C (p.E380A),LDLR c.1322 T＞C (p.A431T)＋c.1867 A＞G (p.I623V), and ABCG5 c.1337 G＞A (p.R447Q). Conclusion: LDLR andAPOB, but notPCSK9, mutations were the major genetic causes of FH. Four novel mutations inLDLR orABCG5 were identified. This genetic screening method using mass spectrometry, targeted NGS, and MLPA analysis provided an efficient algorithm for genetic testing for clinically diagnosed FH in Taiwan.

Polygenic risk scores for low-density lipoprotein cholesterol and familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant monogenic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of premature coronary artery disease (CAD). Recently, it has been shown that a high polygenic risk score (PRS) could be an independent risk factor for CAD in FH patients of European ancestry. However, it is uncertain whether PRS is also useful for risk stratification of FH patients in East Asia. We recruited and genotyped clinically diagnosed FH (CDFH) patients from the Kanazawa University Mendelian Disease FH registry and controls from the Shikamachi Health Improvement Practice genome cohort in Japan. We calculated PRS from 3.6 million variants of each participant (imputed from the 1000 Genome phase 3 Asian dataset) for LDL-C (PRSLDLC) using a genome-wide association study summary statistic from the BioBank Japan Project. We assessed the association of PRSLDLC with LDL-C and CAD among and within monogenic FH, mutation negative CDFH, and controls. We tested a total of 1223 participants (376 FH patients, including 173 with monogenic FH and 203 with mutation negative CDFH, and 847 controls) for the analyses. PRSLDLC was significantly higher in mutation negative CDFH patients than in controls (p = 3.1 × 10-13). PRSLDLC was also significantly linked to LDL-C in controls (p trend = 3.6 × 10-4) but not in FH patients. Moreover, we could not detect any association between PRSLDLC and CAD in any of the groups. In conclusion, mutation negative CDFH patients demonstrated significantly higher PRSLDLC than controls. However, PRSLDLC may have little additional effect on LDL-C and CAD among FH patients.

Familial Hypercholesterolemia in Asia Pacific: A Review of Epidemiology, Diagnosis, and Management in the Region.

Familial hypercholesterolemia (FH) is a common genetic disease that is estimated to affect at least 15 million people in the Asia Pacific region. Affected individuals are at significantly increased risk of premature atherosclerotic cardiovascular disease. A literature review was undertaken to provide an overview of the epidemiology, diagnosis, and management of FH across the region.Currently, epidemiological data relating to FH are lacking across the Asia Pacific. Of the 15 countries and regions considered, locally conducted studies to determine FH prevalence were only identified for Australia, China, India, and Japan. Although practically all national clinical guidelines for dyslipidemia include some commentary on FH, specific guidelines on the management of FH are available for only one third of the countries and regions evaluated. Estimates of current FH diagnosis rates suggest that most affected individuals remain undiagnosed and untreated. Although innovative medications such as proprotein convertase subtilisin/kexin type 9 inhibitors have been approved and are available in most countries and regions considered, they are currently reimbursed in only one quarter.Despite these shortcomings, there is cause for optimism. Early experience with cascade screening in Hong Kong, India, and Vietnam has proven an effective means of identifying family members of probands, as has a reverse screening of family members of children with FH in China. FH registries are gaining momentum across the region, with registries now established in almost half of the countries and regions evaluated. This review concludes with a Call to Action on FH for Asia Pacific to engage healthcare professionals, improve public awareness, and form national FH alliances, comprising all relevant healthcare professional organizations, as a platform to expedite national quality improvement programs in the management of FH.

Prevalence of Non-coronary Heart Disease in Patients with Familial Hypercholesterolemia: An Analysis from the HELLAS-FH.

Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH. This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range - IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respectively. NAFLD was present in 24% of study participants. HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population.

Addressing Gaps in Racial/Ethnic Representation in Familial Hypercholesterolemia Registries: Implications and Recommendations for Equitable Access to Research and Care.

Addressing Gaps in Racial/Ethnic Representation in Familial Hypercholesterolemia Registries: Implications and Recommendations for Equitable Access to Research and Care.

Patient Perspectives Regarding Genetic Testing for Familial Hypercholesterolemia

BackgroundFamilial hypercholesterolemia (FH) is a common genetic disorder resulting in high levels of low-density lipoprotein cholesterol and increased risk of atherosclerotic cardiovascular disease. Genetic testing for FH is recommended but is not available in most of Canada. Consequently, there is a paucity of data regarding patient experiences with genetic testing. The objectives of this study were to investigate the attitudes and perspectives of patients with FH who underwent genetic testing. MethodsWe administered an anonymous online survey to participants in the British Columbia Familial Hypercholesterolemia Registry who had undergone research-based genetic testing for FH. The survey included 25 questions and explored patients’ experiences with the genetic testing process, willingness to recommend genetic screening, and motivation to lower cholesterol levels. ResultsAmong 183 respondents, 38 (20.7%) had a positive genetic test result, 27 (14.8%) had a negative result, and 118 (64.4%) were awaiting their results. Compared with individuals awaiting their test results, participants with a positive genetic test were more likely to believe lipid-lowering therapy was highly important (74.3% vs 55.4%; P = 0.05). They were also more likely to strongly agree that a diagnosis of FH was important to them (71.1% vs 46.2%; P = 0.008), and were more likely to recommend genetic screening to their family members (85.9% vs 72.9%; P = 0.04). ConclusionsTo our knowledge, this is the first study in Canada to explore the perspectives of patients with FH who underwent genetic testing. These results suggest that genetic testing for FH might offer benefits in important patient-centred outcomes.

Predictors of cardiovascular outcomes in patients with heterozygous familial hypercholesterolemia according the russian familial hypercholesterolemia registry

Predictors of cardiovascular outcomes in patients with heterozygous familial hypercholesterolemia according the russian familial hypercholesterolemia registry

Gender specificities of the Ukrainian familial hypercholesterolemia registry

Background and Aims: To estimate gender-specific differences of patients with possible familial hypercholesterolemia (FH) (LDL-C ≥ 5 mmol/l) based on the data of the Ukrainian FH Registry.