Relations of physical signs to genotype, lipid and inflammatory markers, coronary stenosis or calcification, and outcomes in patients with heterozygous familial hypercholesterolemia

Abstract Background Although the presence of physical signs [tendon xanthomas and/or corneal arcus (TX/CA)], are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH. Methods LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. Laboratory markers (proprotein convertase subtilisin/kexin type 9 [PCSK9], lipoprotein(a) and high-sensitivity C-reactive protein [hsCRP]), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed. Results Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels; higher PCSK9 or hsCRP concentrations; more LDLR positive mutations; and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p < 0.001). Patients with physical signs and mutation positivity had threefold higher risks of CVEs (adjusted hazard ratio 3.34, 95% confidence interval 1.04–10.72, p = 0.024). Conclusions Physical signs were associated with genotypes and phenotypes, and worse outcomes in patients with HeFH, suggesting that these signs may help in risk stratification in these patients.

Download Full-text

The Clinical Outcomes Based on the Achievement of Low-Density Lipoprotein Cholesterol Targets after ST Elevation Myocardial Infarction

Journal of Clinical Medicine ◽

10.3390/jcm9010079 ◽

2019 ◽

Vol 9 (1) ◽

pp. 79

Author(s):

Wei-Chieh Lee ◽

Chih-Yuan Fang ◽

Chien-Jen Chen ◽

Cheng-Hsu Yang ◽

Chiung-Jen Wu ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Left Main Coronary Artery ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Left Main ◽

Main Coronary Artery Disease ◽

Group 2 ◽

Artery Disease

The clinical outcome of patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), with or without achievement of low-density lipoprotein cholesterol (LDL-C) targets, has rarely been investigated. This study was performed to investigate the comparison of clinical outcome in STEMI patients with or without achievement LDL-C targets (below 70 mg/dL and/or ≥50% reduction). Between November 2013 and December 2016, 689 STEMI patients underwent primary PCI in our hospital. Patients who were deceased, lost to follow-up, had no follow-up lipid profile, or had no side effects after statin use were excluded. A total of 343 patients were classified into group 1 (with LDL-C target achievement) and 172 patients were classified into group 2 (without LDL-C target achievement). Between the two groups, a higher prevalence of left main coronary artery disease, smaller pre-PCI stenosis, and a larger pre-PCI minimal luminal diameter were noted in group 2. The incidence of post-MI angina (8.7% vs. 6.4%; p = 0.393), target vessel revascularization (2.3% vs. 3.5%; p = 0.566), and recurrent MI (1.5% vs. 1.2%; p = 1.000), showed similar results between the two groups during a one-year follow-up period. Initial LDL-C levels ≥130 mg/dL, left main coronary artery disease, and absence of diabetes mellitus were positively associated with non-achievement of LDL-C targets. After STEMI, 66.6% of patients could achieve LDL-C targets one year later. However, such patients did not show better clinical outcomes. Non-DM, initial LDL-C levels ≥130 mg/dL, and left main coronary artery disease were related to non-achievement of LDL-C targets.

Download Full-text

The Prevalence of Heterozygous Familial Hypercholesterolemia in Selected Regions of the Russian Federation: The FH-ESSE-RF Study

Journal of Personalized Medicine ◽

10.3390/jpm11060464 ◽

2021 ◽

Vol 11 (6) ◽

pp. 464

Author(s):

Alexey N. Meshkov ◽

Alexandra I. Ershova ◽

Anna V. Kiseleva ◽

Svetlana A. Shalnova ◽

Oxana M. Drapkina ◽

...

Keyword(s):

Familial Hypercholesterolemia ◽

Russian Federation ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density Lipoprotein Cholesterol ◽

Pcsk9 Inhibitor ◽

Heterozygous Familial Hypercholesterolemia ◽

Lipid Clinic ◽

The Russian Federation ◽

Artery Disease

Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic conditions but remains substantially underdiagnosed. The aim of our study was to investigate the prevalence of HeFH in the population of 11 different regions of Russia. Individuals were selected from the Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study. All participants who had low-density lipoprotein cholesterol (LDL-C) higher than 4.9 mmol/L, or LDL-C lower than 4.9 mmol/L, but had statin therapy, were additionally examined by FH experts. FH was diagnosed using the Dutch Lipid Clinic Network criteria, incorporating genetic testing. HeFH prevalence was assessed for 18,142 participants. The prevalence of patients with definite or probable HeFH combined was 0.58% (1 in 173). A total of 16.1% of patients with definite or probable HeFH had tendon xanthomas; 36.2% had mutations in one of the three genes; 45.6% of FH patients had coronary artery disease; 63% of HeFH patients received statins; one patient received an additional PCSK9 inhibitor; no patients received ezetimibe. Only 3% of patients reached the LDL-C goal based on 2019 ESC/EAS guidelines. Underdiagnosis and undertreatment of FH in Russia underline the need for the intensification of FH detection with early and aggressive cholesterol-lowering treatment.

Download Full-text

Effects of ABCA1 gene polymorphisms on risk factors, susceptibility and severity of coronary artery disease

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-136917 ◽

2020 ◽

Vol 96 (1141) ◽

pp. 666-673

Author(s):

Zhan Lu ◽

Zhi Luo ◽

Aimei Jia ◽

Irfan Muhammad ◽

Wei Zeng ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Stenosis ◽

Low Density Lipoprotein ◽

Coronary Vessels ◽

Density Lipoprotein ◽

Gensini Score ◽

Risk Alleles ◽

Hs Crp ◽

Artery Disease

BackgroundThe relationships between the rs1800976, rs4149313 and rs2230806 polymorphisms in ATP binding cassette protein A1 and severity of coronary artery disease (CAD) remain unclear.MethodsFour hundred and forty-two patients with CAD and 217 CAD-free subjects were enrolled in this study. The rs1800976, rs4149313 and rs2230806 polymorphisms were genotyped by PCR-RFLP. Severity of CAD was evaluated by Gensini score system, number of stenotic coronary vessels and extent of coronary stenosis.ResultsC allele of the rs1800976 polymorphism, G allele of the rs4149313 polymorphism and A allele of the rs2230806 polymorphism were found to be risk alleles for CAD (p<0.05 for all). In patients with CAD, C allele of the rs1800976 polymorphism was associated with high levels of hypersensitive C reactive protein (hs-CRP) and cystatin c (CysC), and its frequency increased with percentiles of Gensini score, number of stenotic coronary vessels and extent of coronary stenosis (p<0.05 for all). The subjects with GA genotype of the rs4149313 polymorphism had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and hs-CRP than those with AA genotype (p<0.05 for all). The subjects with AA genotype of the rs2230806 polymorphism had higher levels of TC, LDL-C and uric acid than those with GA genotype (p<0.05 for all). No associations between the rs4149313 or rs2230806 polymorphism and severity of CAD were detected.ConclusionsThe rs1800976 polymorphism is significantly associated with the occurrence and severity of CAD, which is possibly mediated by hs-CRP and CysC.

Download Full-text

A Case of Severe Carotid Stenosis in a Patient with Familial Hypercholesterolemia without Significant Coronary Artery Disease

Case Reports in Cardiology ◽

10.1155/2014/853921 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

Marcos Aurélio Lima Barros ◽

Hygor Ferreira-Fernandes ◽

Ingrid Cristina Rêgo Barros ◽

Adriel Rêgo Barbosa ◽

Giovanny Rebouças Pinto

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Carotid Stenosis ◽

Familial Hypercholesterolemia ◽

Low Density Lipoprotein ◽

Significant Coronary Artery Disease ◽

Density Lipoprotein ◽

Cholesterol Levels ◽

Artery Disease ◽

Heterozygous Form

Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by elevated low-density lipoprotein cholesterol levels in the blood. In its heterozygous form, it occurs in 1 in 500 individuals in the general population. It is an important contributor to the early onset of coronary artery disease (CAD), accounting for 5–10% of cases of cardiovascular events in people younger than 50 years. Atherogenesis triggered by hypercholesterolemia generally progresses faster in the coronary arteries, followed by the subsequent involvement of other arteries such as the carotids. Thus, symptoms of CAD commonly appear before the onset of significant carotid stenosis. Herein, we report the case of a patient with untreated FH who had severe carotid atherosclerosis at the age of 46 years but had no evidence of significant CAD.

Download Full-text

An Uncommon Association of Sever Early Coronary Artery Disease and Aortic Coarctation in Patient with Familial Hypercholesterolemia: A Case Report

10.22541/au.161893335.54476252/v1 ◽

2021 ◽

Author(s):

HANI ALKATTAN ◽

Ahmed Aljizeeri ◽

Ahmed Arifi

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Familial Hypercholesterolemia ◽

Coronary Artery Bypass Surgery ◽

Artery Bypass ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Coarctation Of The Aorta ◽

Inherited Disease ◽

Artery Disease

Familial hypercholesterolemia is a rare inherited disease that results in elevated levels of low-density lipoprotein (LDL) and clinically leads to early coronary artery disease. It is rare for this disease to be associated with the coarctation of the aorta. In this report, we review the clinical case of an 18-year-old who was referred to our center with angina pectoris manifestation. A comprehensive clinical and investigative evaluation of the patient pre-operatively showed the presence of familial hypercholesterolemia, Coarctation of the aorta, and ischemic cardiomyopathy that required coronary artery bypass surgery.

Download Full-text