Tag Archives: atherosclerosis

The utility of MLPA in Familial Hypercholesterolemia diagnosis

DOI: 10.2478/amma-2021-0021

Background: Familial Hypercholesterolemia (FH) is an inherited disease, associated with an increased risk of atherosclerosis, manifested clinically as premature coronary heart disease. FH is biochemically characterized by increased Cholesterol and Low-density Lipoprotein Cholesterol serum levels. The diagnosis is often made using clinical scores however, the definitive FH diagnosis should point out the underlying molecular change, which can be: a point mutation within the three major genes, a number of single nucleotide polymorphisms determining the polygenic etiology, or copy number variations in the Low-density lipoprotein receptor gene.
Objective: In the present study we investigated copy number variations as a possible etiological factor for FH in a cohort of patients with documented premature coronary heart disease.
Methods: The study population consisted of 150 patients with premature coronary heart disease documented by angiography, all being under lipid-lowering therapy, and 20 apparently healthy controls. Serum lipids were assessed using the Cobas Integra 400 plus and commercial reagents. Copy number variations were evaluated with the SALSA MLPA Probemix P062 LDLR kit.
Results: Cholesterol, Triglycerides, Low-density Lipoprotein Cholesterol and High-density Lipoprotein Cholesterol showed no difference between patients and controls. No copy number variations were detected in the investigated regions, namely all 18 exons and the promoter region of the Low-density lipoprotein receptor gene.
Conclusions: Even in the presence of negative results, the Familial Hypercholesterolemia genetic diagnosis has to be further pursued in the presence of a clinical diagnosis, as the identification of the molecular etiology may bring additional clinical and therapeutical benefits, as well as open the possibility for “cascade screening”.

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Markers of Atherosclerosis in Hypertensive Patients with Less Advanced Chronic Kidney Disease

DOI: 10.2478/amma-2019-0022

Objective: Our study aimed to validate the neutrophil-to-lymphocyte ratio (NLR) as a marker for aortic arch calcification in hypertensive patients with less advanced chronic kidney disease (CKD).
Methods: A number of forty-four hypertensive patients with chronic kidney disease (categories G3a and G3b – 2012 KDIGO nomenclature) were included in the study. Considering the presence of aortic arch calcification (AAC) on chest X-ray, the study population was divided into two groups: 27 patients AAC present and seventeen without aortic arch calcification. Laboratory data were collected for each patient and NLR was computed. Comorbidities were also recorded: stable coronary artery disease, lower extremity arterial disease and hypertensive heart disease.
Results: A positive correlation between neutrophil-to-lymphocyte ratio and aortic arch calcification in hypertensive CKD patients was identified. Furthermore, advanced age, increased alkaline phosphatase and increased erythrocyte sedimentation rate had a positive association with aortic arch calcification. We found no statistical correlation between neutrophil-to-lymphocyte ratio and other laboratory features in both groups of patients.
Conclusions: Neutrophil-to-lymphocyte ratio may be viewed as a potential risk factor for vascular calcification in patients with moderate chronic kidney disease; nevertheless, future extensive studies are necessary. In the management of hypertensive patients, general medicine might particularly benefit of this simple, readily available inflammatory marker.

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MTHFR – Ala222Val Effects on Metabolic Syndrome Progression

DOI: 10.2478/amma-2018-0009

Objective: Methylene-tetrahydrofolate reductase (MTHFR) is involved in adapting metabolism to environmental challenges by various mechanisms, including the control of gene expression by epigenetic and post-translational changes of transcription factors. Though a metabolic syndrome candidate gene, association studies of its common polymorphism rs1801133 (MTHFR-Ala222Val) remain inconclusive with important ethnic differences, and the effect on disease progression was not addressed.
Methods: 307 middle-aged metabolic syndrome patients in a central Romanian hospital setting were investigated metabolically, and genotyped by PCR-RFLP. Disease progression was assessed by the age of onset of metabolic components, as well as development of non-alcoholic fatty liver disease and atherosclerotic complications.
Results: The minor allele frequency of rs1801133 was 30.13%. Metabolic parameters showed no statistically significant differences according to genotype, but variant carriers developed dysglycemia and dyslipidemia earlier (53.28±10.8 vs 59.44±9.31 years, p<0.05 and 58.57±11.31 vs 64.72±10.6 years, p<0.1).While the polymorphism did not influence hepatic complications, an inverse association was found for manifest atherosclerosis (OR=0.49, p=0.006, 95%CI:0.29-0.81), which may be folate-status dependent, and needs further investigations. Simultaneous analysis with transcription factor polymorphisms (rs1801282, rs8192678) showed that the more protective genotypes were present the later metabolic disturbances developed, and in the presence of the other two variants the apparent protective cardiovascular effect disappeared.
Conclusions: The common functional polymorphism rs1801133 may influence metabolic syndrome progression, the age of onset of components and development of atherosclerotic complications. Besides simple additive effects, complex mitigating and aggravating variant interactions may exist, and the protective or predisposing outcome may depend on modifiable environmental factors.

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Correlations Between the Gradient of Contrast Density, Evaluated by Cardio CT, and Functional Significance of Coronary Artery Stenosis

DOI: 10.1515/amma-2015-0119

Background: Assessment of the hemodynamic significance of a coronary artery stenosis is a challenging task, being extremely important for the establishment of indication for revascularization in atherosclerotic coronary artery stenosis. The aim of this study was to evaluate the role of a new marker reflecting the functional significance of a coronary artery stenosis, represented by the attenuation degree of contrast density along the stenosis by Coronary CT.
Material and Method: We evaluated retrospectively 30 patients with angina and coronary luminal narrowing, who underwent 64-slice Coronary Computed Tomography Angiography. We measured the stenosis degree, intraluminal contrast density (Hounsfield units [HU]) at two levels, proximal and distal to stenosis, and the attenuation gradient was calculated on this basis.
Results: The average contrast density was 77,96 UH proximal to the stenosis and 67,6 UH distal to the stenosis. The average transluminal gradient was 10,36. The average length of the coronary lesions was 16,93 mm. In those lesions with significant stenosis, expressed by >70% luminal narrowing, we recorded a significantly higher transluminal attenuation gradient as compared to those with <70% luminal narrowing (6.16 +/-3.7, 95%CI 4.3-80 vs 16.6 +/- 8.4, 95% CI 11.3 – 21.9). The degree of luminal narrowing significantly correlated with the contrast attenuation gradient (r=0.71, p<0.001).
Conclusions: The assessment of intraluminal contrast density by Coronary Computed Tomography Angiography may represent a new noninvasive tool to obtain relevant information about the clinical significance of a coronary stenosis. Larger studies are requested to emphasize the benefits brought by CCTA in evaluating coronary lesions.

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