Familial hypercholesterolaemia (FH) is a rare disease that tends to be diagnosed lately. In Russia, the genetic and phenotypic characteristics of the disease are not well defined. We investigated 102 patients with definite FH. In 52 of these patients (50.9%) genetic analysis was performed, revealing pathogenic mutations of the low density lipoprotein (LDL) receptor gene in 22 patients. We report here five mutations of the LDL receptor gene found in the Karelian FH sample for the first time. The detection rate of mutations in definite FH patients was 42.3%. Two groups of patients with a definite diagnosis of FH according to the Dutch Lipid Clinic Network criteria were compared: the first group had putatively functionally important LDL receptor gene mutations, while in the second group LDL receptor gene mutations were excluded by single-strand conformation polymorphism analysis. Total and LDL cholesterol levels were higher in the group with LDL receptor mutations compared to the mutation-free population. The frequency of mutations in patients with LDL cholesterol > 6.5 mmol/L was more than 3 times higher than that in patients with LDL < 6.5 mmol/L. Total and LDL cholesterol levels and the frequency of coronary heart disease and myocardial infarction were higher in the group with definite FH compared to groups with probable and possible FH. Cholesterol figures in FH patients of different age and sex from the Karelian population were comparable.
The purpose of this study was to examine the pulse wave velocity, aortic augmentation index corrected for heart rate 75 (AIx@75), and central systolic and diastolic blood pressure during 24-hour monitoring in normotensive volunteers. Overall, 467 subjects (206 men and 261 women) were recruited in this study. Participants were excluded from the study if they were less than 19 years of age, had blood test abnormalities, had a body mass index greater than 2 7.5 kg/m2, had impaired glucose tolerance, or had hypotension or hypertension. Ambulatory blood pressure monitoring (ABPM) with the BPLab® device was performed in each subject. ABPM waveforms were analyzed using the special automatic Vasotens® algorithm, which allows the calculation of pulse wave velocity, AIx@75, central systolic and diastolic blood pressure for “24-hour”, “awake”, and “asleep” periods. Circadian rhythms and sex differences in these indexes were identified. Pending further validation in prospective outcome-based studies, our data may be used as preliminary diagnostic values for the BPLab ABPM additional index in adult subjects.
The transcript levels of circadian rhythm genes CLOCK, BMAL1, and PER1 in buccal epithelial cells of the patients with essential arterial hypertension was analyzed in relation to polymorphic variants of CLOCK and BMAL1 genes. These levels were assessed with realtime PCR method at daily hours 9, 13, and 17. The significant differences were revealed in transcript levels of the examined genes in patients with various genotypes at the polymorphic markers 3111TC and 257TG regulatory regions of CLOCK gene. The study detected no significant differences among the carriers of various genotypes at polymorphic markers 862TC and 2121GA of CLOCK gene and 56445TC of BMAL1 gene.
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.
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