familial hypercholesterolemia
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Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 153
László Madar ◽  
Lilla Juhász ◽  
Zsuzsanna Szűcs ◽  
Lóránt Kerkovits ◽  
Mariann Harangi ◽  

Familial hypercholesterolemia (FH) is one of the most common autosomal, dominantly inherited diseases affecting cholesterol metabolism, which, in the absence of treatment, leads to the development of cardiovascular complications. The disease is still underdiagnosed, even though an early diagnosis would be of great importance for the patient to receive proper treatment and to prevent further complications. No studies are available describing the genetic background of Hungarian FH patients. In this work, we present the clinical and molecular data of 44 unrelated individuals with suspected FH. Sequencing of five FH-causing genes (LDLR, APOB, PCSK9, LDLRAP1 and STAP1) has been performed by next-generation sequencing (NGS). In cases where a copy number variation (CNV) has been detected by NGS, confirmation by multiplex ligation-dependent probe amplification (MLPA) has also been performed. We identified 47 causal or potentially causal (including variants of uncertain significance) LDLR and APOB variants in 44 index patients. The most common variant in the APOB gene was the c.10580G>A p.(Arg3527Gln) missense alteration, this being in accordance with literature data. Several missense variants in the LDLR gene were detected in more than one index patient. LDLR variants in the Hungarian population largely overlap with variants detected in neighboring countries.

2022 ◽  
Jinchun He ◽  
Yaodong Wang ◽  
Yanpei Zhang ◽  
Zhijie He

Abstract (1) Background: Studies have suggested that age and the serum total cholesterol (TC) concentration are independent risk factors for cardiovascular disease (CVD) in patients with familial hypercholesterolemia (FH); however, the relationship between age and TC in patients with FH is unclear. We aimed to investigate the correlation between age and TC in patients with FH. (2) Methods: In this retrospective, controlled not matched analysis, a total of 103 patients with FH and 106 non-FH controls were recruited into the study from 2004 to 2017. Spearman and partial correlation analyses, as well as multiple regression analyses, were used to evaluate the relationship between TC and age. (3) Results: There were no significant differences in age, gender, or BMI between the FH group and the control group (p > 0.05). Family history of CVD, TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), lipoprotein (a) (Lp(a)) and non-HDL-C levels were significantly higher in patients with FH compared to the control (p < 0.01). Additionally, the serum TC levels for ages ≥ 50 years were significantly higher than those for ages < 50 years (p < 0.05) in FH patients. In both Spearman and partial correlation analyses, age was found to be significantly correlated with serum TC (p < 0.001) in the FH group but not in the control group, which was confirmed by further multiple linear regression analyses and logistic regression analyses. (4) Conclusions: Age is an independent factor influencing serum TC level in patients with FH, and it is necessary to conduct early screening and early intervention.

2022 ◽  
Vol 17 (4) ◽  
pp. 74-78
N. G. Lozhkina ◽  
A. N. Spiridonov

Familial hypercholesterolemia is a hereditary autosomal dominant disease characterized by a violation of cholesterol metabolism. This nosology was first described in the late 1930s by the Norwegian clinician Karl Moeller, he proposed the idea that hypercholesterolemia and tendon xanthomas are associated with cardiovascular diseases through the inheritance of a single gene. In 1964, two clinical phenotypes of familial hypercholesterolemia were discovered: heterozygous and homozygous, associated with an unfavorable prognosis. To date, it is known that the long-running process of accumulation of low-density lipoproteins in the intima of blood vessels may not have clinical symptoms for many years due to the developed system of collaterals and the absence of hemodynamically significant stenosis. However, without timely diagnosis and appropriate therapy, this condition inevitably leads to the development of a cardiovascular event. The article presents a clinical case demonstrating the development of myocardial infarction in a patient with a late diagnosis of this disease.

2022 ◽  
Emil Jørsboe ◽  
Mette Korre Andersen ◽  
Line Skotte ◽  
Frederik Filip Stæger ◽  
Nils Joakim Kaas Færgeman ◽  

Background: The common Arctic specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this we aimed to investigate the effect of p.G137S on metabolic health, and cardiovascular disease risk among Greenlanders to quantify its impact on the population. Methods: In a population based Greenlandic cohort (n=5063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. Additionally, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n=1629). Results: 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischaemic heart disease (HR (95% CI), 1.51 (1.18-1.92), P=0.00096), peripheral artery disease (1.69 (1.01-2.82), P=0.046), and coronary operations (1.78 (1.21-2.62), P=0.0035). Conclusions: Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.

2022 ◽  
Vol 23 (1) ◽  
pp. 1
Nicola Marziliano ◽  
Alessandro Medoro ◽  
Stefano Folzani ◽  
Mariano Intrieri ◽  
Claudio Reverberi

2022 ◽  
Vol 12 (1) ◽  
pp. 71
Victoria Korneva ◽  
Tatyana Kuznetsova ◽  
Ulrich Julius

In patients with familial hypercholesterolemia (FH) the exposure of very high LDL-C concentration and cumulative LDL-C level (cum LDL-C) can play a significant role in the prognosis. Objective: to analyze the contribution of “cum LDL-C for all life” and the index “cum LDL-C/age” to the development of coronary heart disease (CHD), myocardial infarction (MI), and a combined end point: MI, stroke, unstable angina in FH patients. Methods: 188 patients (mean age 49.2 years, males 45.7%) with FH were examined (Dutch Lipid Clinic Criteria). We had evaluated cumulative LDL-C and index “cum DL-C/age” along with other classical risk factors. Cum LDL-C was calculated as LDL-Cmax × (age at initiating of hypolipidemic therapy) + LDL-C at inclusion age at initiation/correction therapy). Cumulative LDL-C and “cum LDL-C/age” were calculated as the ratio cum LDL-C to age. The follow-up period was 5.4 (from 3 to 10) years. Results: The index “cum LDL-C/age” was higher in patients with CHD 58.7 ± 10.4 mmol/L/years vs. 40.1 ± 11.7 mmol/L/years in patients without CHD (p < 0.001). According to our data based on the results of the logistic regression analysis in patients with FH, cumulative LDL-C and the cumulative index “cum LDL–C/age” played a strong predictive role in the development of CHD in FH patients; it was greater than the role of TC and LDL-C concentrations. We present ROC curves for CHD, MI and combined end point in FH patients, and a prognostic scale for CHD development, which is based on classical cardiovascular risk factors. Conclusion: cumulative LDL-C level plays an important role in the development of CHD in FH patients.

Krishna Kumar B. Pillai ◽  
Swarup A. V. Shah ◽  
Lakshmi Lavanya Reddy ◽  
Tester F. Ashavaid ◽  
Sunitha Vishwanathan

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