Diagnosis Of Familial Hypercholesterolemia In The Clinical Practice: Performance Of Dutch Lipid Clinic Network Score

The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3–5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% (n = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold (p < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies.

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Classification of malnutrition in cystic fibrosis: implications for evaluating and benchmarking clinical practice performance

American Journal of Clinical Nutrition ◽

10.1093/ajcn/88.1.161 ◽

2008 ◽

Vol 88 (1) ◽

pp. 161-166 ◽

Cited By ~ 28

Author(s):

HuiChuan J Lai ◽

Suzanne M Shoff

Keyword(s):

Cystic Fibrosis ◽

Clinical Practice ◽

Practice Performance

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Estimated Prevalence of Familial Hypercholesterolemia Among Egyptian Patients with Acute Coronary Syndromes; Analysis from The Cardiorisk Project

European Heart Journal Supplements ◽

10.1093/eurheartj/suab069.006 ◽

2021 ◽

Vol 23 (Supplement_D) ◽

Author(s):

Ashraf Reda ◽

Ahmed Bendary ◽

Ahmed Shawky Elserafy ◽

Elsayed Farag ◽

Tamer Mostafa ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Acute Coronary Syndromes ◽

Total Population ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cross Sectional ◽

Lipid Clinic ◽

Egyptian Patients ◽

Coronary Syndromes ◽

Premature Cad

Abstract Aims The prevalence of familial hypercholesterolemia (FH) in Egypt is largely un- known. We aimed to estimate the prevalence of FH among 3224 Egyptian patients with acute coronary syndromes enrolled from 2015 to 2018 in the nationwide cross- sectional cardioRisk project. Methods and Results We applied the Dutch Lipid Clinic criteria for the diagnosis of FH on the available data recorded for the patients enrolled in the CardioRisk project. Two main criteria were applied: the presence of premature CAD (given 2 points in the Dutch criteria), and the categorized low density lipoprotein cholesterol (LDL-C) lev- els (given 1, 3, 5, or 8 points in the Dutch criteria according to the level). From a total of 3224 patients, 2743 patients had available LDL-C levels. Among those patients, when applying the abovementioned 2 criteria, we estimated that 472 patients had at least ‘possible’ FH (17.2% of the total population). Specifically, 4 patients had ‘defi- nite’ FH (0.1%), 7 patients had ‘probable’ FH (0.25%), and 461 patients had ‘possi- ble’ FH (16.8%). Conclusion The estimated prevalence of at least ‘possible’ FH among Egyptian patients with ACS is 17%.

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Abstract 14681: Comparative Study Between International Guidelines in Detecting Pediatric Familial Hypercholesterolemia Through a Unique Community Health System in Kagawa, Japan

Circulation ◽

10.1161/circ.142.suppl_3.14681 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Keiji Matsunaga ◽

Asako Mizobuchi ◽

Hayato Tada ◽

Tsuyoshi Sasaki ◽

Yoshihiro Asano ◽

...

Keyword(s):

Health System ◽

Community Health ◽

Familial Hypercholesterolemia ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hereditary Disease ◽

International Guidelines ◽

Number Of Children ◽

Lipid Clinic ◽

Lipid Screening

Introduction: Familial hypercholesterolemia (FH) is an autosomal hereditary disease found in patients who have elevated low-density lipoprotein cholesterol (LDL-C) from birth. Early detection and treatment of FH during childhood potentially reduces the risk of premature cardiovascular events. In Kagawa prefecture, a unique community health system, involving three steps, has been conducted to prevent lifestyle-related diseases for 10-year-old children. This system includes universal lipid screening, selection by pediatricians, and next-generation sequencing (NGS) of FH-related genes in hospitals. The aim of this study is to compare 3 international guidelines to detect pediatric FH with this unique community health system in Kagawa. Methods: In Kagawa prefecture, the universal lipid screening of approximately 8,000 children at 10 years of age is performed annually, covering over 90% of the target group. After excluding secondary hypercholesterolemia, pediatric clinics introduced children with LDL-C >140mg/dL to 4 designated hospitals to perform NGS. We applied the guidelines of the Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), and the Japanese Atherosclerosis Society (JAS) to children who received NGS in the unique community health system in Kagawa. Results: We performed NGS for 46 children from January 2018 to February 2020 (LDL-C 186.0±50.3 mg/dL; Male/F 27/19) and 26 (57%) had FH genetic mutations (23 LDL-R and 3 PCSK9 mutations). Seventeen children met FH criteria for DLCN (35%), 10 for Simon Broome (22%), and 11 for JAS (24%), respectively. The combination of NGS and either of the 3 guidelines increased the number of children diagnosed as FH up to 31 (67%). Conclusion: International guidelines detected only half of pediatric FH who were diagnosed by the unique community health system in Kagawa. Further investigation will be required to build an effective universal screening system for pediatric FH.

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Differences in phenotype, genotype and cardiovascular events between patients with probable and definite heterozygous familial hypercholesterolemia

Personalized Medicine ◽

10.2217/pme-2018-0135 ◽

2019 ◽

Vol 16 (6) ◽

pp. 467-478

Author(s):

Ye-Xuan Cao ◽

Bing-Yang Zhou ◽

Di Sun ◽

Sha Li ◽

Yuan-Lin Guo ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Cardiovascular Events ◽

Oxidized Ldl ◽

Low Density Lipoprotein ◽

Survival Rates ◽

Gene Mutations ◽

Density Lipoprotein ◽

Heterozygous Familial Hypercholesterolemia ◽

Lipid Clinic ◽

Kaplan Meier

Aim: To investigated the potential differences between probable and definite heterozygous familial hypercholesterolemia (HeFH) patients diagnosed by Dutch Lipid Clinic Network criteria. Methods: Clinical characteristics, lipid profile, severity of coronary artery stenosis and gene mutations were compared. Kaplan–Meier curve was performed to evaluate the cardiovascular events. Results: Overall, 325 participants were included and divided into two groups: probable (n = 233) and definite HeFH (n = 92). Definite HeFH patients had higher low-density lipoprotein cholesterol (LDL-C), oxidized-LDL and proprotein convertase subtilisin/kexin 9 levels, and higher prevalence of tendon xanthomas. The incidence of genetic mutations was statistically higher in definite HeFH than probable HeFH patients. The coronary stenosis calculated by Gensini score was statistically severer in definite HeFH patients. The best LDL-C threshold for predicting mutations was 5.14 mmol/l. Definite HeFH had lower event-free survival rates. Conclusion: Definite HeFH patients had higher severity of phenotype and genotype, and higher risk of cardiovascular events.

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Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia

Clinical Chemistry ◽

10.1373/clinchem.2005.055228 ◽

2005 ◽

Vol 51 (11) ◽

pp. 2067-2073 ◽

Cited By ~ 41

Author(s):

Daniel T Holmes ◽

Brian A Schick ◽

Karin H Humphries ◽

Jiri Frohlich

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Risk Factor ◽

Familial Hypercholesterolemia ◽

Independent Risk Factor ◽

Independent Predictor ◽

Cvd Risk ◽

Lipoprotein A ◽

Heterozygous Familial Hypercholesterolemia ◽

Lipid Clinic

Abstract Background: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic. Methods: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event. Results: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53–4.39; P <0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79–5.69); P <0.001] and ratio of total to HDL-cholesterol [1.18 (1.07–1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92–2.61) and 1.57 (0.90–2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71–1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH). Conclusion: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.

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