Algorithm for detection and screening of familial hypercholesterolemia in Lithuanian population.

BACKGROUND: Familial hypercholesterolemia (FH) is one of the most common autosomal dominant diseases. FH causes a lifelong increase in low-density lipoprotein cholesterol (LDL-C) levels, which in turn leads to atherosclerotic cardiovascular disease. The incidence of FH is widely underestimated and undertreated, despite the availability and effectiveness of lipid-lowering therapy. Patients with FH have an increased cardiovascular risk; therefore, early diagnosis and treatment are vital. To address the burden of FH, several countries have implemented national FH screening programmes. The currently used method for FH detection in Lithuania is mainly based on opportunistic testing with subsequent cascade screening of index cases' first-degree relatives. METHODS: A total of 428 patients were included in this study. Patients with suspected FH are referred to a lipidology center for thorough evaluation. Patients who met the criteria for probable or definite FH according to the Dutch Lipid Clinic Network (DLCN) scoring system and/or had LDL-C > = 6.5 mmol/l were subjected to genetic testing. Laboratory and instrumental tests, vascular marker data of early atherosclerosis, and consultations by other specialists, such as radiologists and ophthalmologists, were also recorded. RESULTS: A total of 127/428 (30%) patients were genetically tested. FH-related mutations were found in 38.6% (n = 49/127) of the patients. Coronary artery disease (CAD) was diagnosed in 13% (n = 57/428) of the included patients, whereas premature CAD was found in 47/428 (11%) patients. CAD was diagnosed in 19% (n = 9/49) of patients with FH-related mutations, and this diagnosis was premature for all of them. CONCLUSIONS: Most patients in this study were classified as probable or possible FH without difference of age and sex. The median age of FH diagnosis was 47 years with significantly older females than males, which refers to the strong interface of this study with the LitHir programme. CAD and premature CAD were more common among patients with probable and definite FH, as well as those with an FH-causing mutation. The algorithm described in this study is the first attempt in Lithuania to implement a specific tool which allows to maximise FH detection rates, establish an accurate diagnosis of FH, excluding secondary causes of dyslipidaemia, and to select patients for cascade screening initiation more precisely.

Primary Arterial Hypertension Associated with Cognitive Dysfunction in Young Adults: Results from a Cross-Sectional Controlled Study.

Despite evidence of primary hypertension (PH)-associated cognitive dysfunction in pediatric, middle-aged, and older adult populations, respective data in young adults remains scarce. We aimed to define differences in cognitive performance between individuals with PH and healthy controls in early adulthood. A convenience sample of young adults (age 18-45 years) with PH and their healthy sex, age, education, and household income matched counterparts were cross-sectionally tested for verbal fluency, verbal memory, general intelligence, reaction speed, attention, visual memory, and executive functioning. Between-group differences were determined using Student's t and Mann-Whitney U tests. Sensitivity analysis was performed by adjusting for body mass index (BMI) in analysis of covariance (ANCOVA) and regression models. Thirty-three adults with PH (22, 66.7% male, median age 38.8, interquartile range (IQR) = 33.2-41.6 years) and twenty-two healthy controls (9, 40.9% male, median age 36.1, IQR = 27.5-39.8 years) completed the neuropsychological assessment. Participants with PH performed worse on computerized tasks of reaction time (median response time (Z = -2.019, p = 0.044), median time for release of response button (Z = -2.509, p = 0.012)) and sustained attention (signal detection measure, RVPA (t = 2.373, p = 0.021), false alarms ÷ (false alarms + correct rejections), RVPPFA (Z = -2.052, p = 0.040)). The group variable was not a statistically significant predictor of performance in these domains after adjustment for BMI (p > 0.05). In regression analyses, high office systolic blood pressure (oSBP) was independently associated with poor sustained attention (ßSBP(st.) = -0.283, multiple R2 = 0.252 (RVPA), ßSBP(st.) = 0.551, multiple R2 = 0.386 (RVPPFA)). Young adults with PH were found to perform worse in tasks of response speed and sustained attention. While the difference between neuropsychological evaluation results in PH and control groups was confounded by BMI, oSBP measures were independently related to sustained attention. The selectivity of PH-associated cognitive profile in young adults has to be confirmed in larger trials.

Early Atherosclerosis in Familial Hypercholesterolemia Patients: Significance of Vascular Markers for Risk Stratification.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder that manifests as impaired low-density lipoprotein cholesterol (LDL-C) metabolism, resulting in lifelong exposure to high cholesterol levels and increased risk of cardiovascular disease (CVD). There is heterogeneity in cardiovascular risk for FH patients, so risk stratification is of utmost importance. The aim of this study was to evaluate the impact of increases in LDL-C and the impact of other CVD risk factors on vascular markers in the FH patient population. METHODS: A total of 428 patients were included in this study and divided into two groups according to age: ≤40 years in the first group and ≥41 years in the second group. Vascular markers of atherosclerosis included the common carotid artery (CCA) intima-media thickness (IMT), pulse wave velocity (PWV), flow-mediated dilation (FMD), ankle-brachial index (ABI), and cardio-vascular index (CAVI). The influence of traditional CVD risk factors on atherosclerotic changes in vascular markers was analyzed. RESULTS: A statistically significant difference in IMT was detected between the same sex and different age groups (p < 0.001), whereas no significant difference was detected between the sexes within each age group. In the ≤40-year-old group, the mean IMT among males was 612.5 µm (±88.2) and that among females was 580.6 µm (±77.7) (p > 0.05); in the ≥41-year-old group, the mean IMT was 697.4 µm (±138.4) for males and 700.3 µm (±114.4) for females (p > 0.05). Higher LDL-C was associated with greater IMT (r = 0.405; p = 0.009) in the younger age group (≤40 years); however, in the older age group (≥41 years), this correlation was not evident (r = -0.07; p = 0.596). Carotid plaque formation was more common among males (OR = 2.2; 95% CI: 1.2-4.0) and hypertensive patients (OR = 2.7; 95% CI: 1.6-4.7). Age was a mildly significant risk factor for increased ABI (ß = 0.13, p < 0.05). FMD was found to be impaired for all patients, and no risk factors were shown to have further influence. Age was a significant risk factor for increased arterial stiffness, as measured by both the CAVI and PWV. CONCLUSIONS: Although vascular markers of atherosclerosis may provide a unique and valuable way to evaluate cardiovascular risk, the results of this study show that only increased IM thickness could be beneficial for risk stratification in young FH patients, whereas other vascular markers of atherosclerosis would be excessive, as they do not provide merit in risk evaluation in this population.

Aerobic Training Effect on Arterial Stiffness in Metabolic Syndrome.

BACKGROUND: Metabolic syndrome, physical inactivity, and central obesity contribute to early vascular aging, which leads to increased risk of cardiovascular disease. This study aimed to assess the effect of heart rate (HR)-targeted aerobic exercise training on the indices of early vascular aging, in particular, arterial stiffness, and on anthropometric and clinical profile of metabolic syndrome subjects. METHODS: There were 126 metabolic syndrome subjects randomly selected. Anthropometric parameters, blood pressure (BP), blood sample, and arterial wall functional and structural parameters were obtained prior to and after the 8-week (84 patients) supervised training program. The age- and sex-matched control group (42 patients) followed the same protocol, except for the HR-targeted training program. RESULTS: In the study group, HR-targeted training was associated with decreased aortic pulse wave velocity (8.47 ± 1.40 vs 8.01 ± 1.06 m/s; P = .005), HR (P < .001), systolic (P < .015) and diastolic (P < .004) BP, waist circumference (P < .004), total and low-density-lipid cholesterol (respectively, 6.42 ± 1.41 vs 5.89 ± 1.32, P = .003 and 4.2 ± 1.18 vs 3.8 ± 1.21, P = .002), and an increase in aerobic capacity (P < .001). In the control group there were no statistically significant changes of arterial stiffness parameters. Multivariate analysis revealed that reduction of arterial stiffness was BP dependent. CONCLUSIONS: In subjects with metabolic syndrome, HR-targeted exercise training is associated with BP-dependent decrease in aortic stiffness and improvement of metabolic and fitness parameters.

Effect of ileal infusion of short-chain fatty acids on pancreatic prandial secretion and gastrointestinal hormones in pigs.

OBJECTIVES: Nutrients passing the ileum induce mechanisms regulating pancreatic secretion, but the effect of short-chain fatty acids (SCFAs) present in the ileum because of either intestinal fermentation or due to the cecoileal reflux is still unclear. This study investigated the effect of ileal SCFAs on pancreatic secretion and plasma levels of peptide YY, cholecystokinin, motilin, and neurotensin. METHODS: The pigs were fitted with pancreatic duct, ileal, and jugular vein catheters, and a duodenal T-shaped cannula. Saline, 85.0 or 170.0 mM acetate, 5.0 or 10.0 mM butyrate, 7.5 or 15.0 mM propionate were infused into the ileum during feeding. RESULTS: The ileal infusions of SCFAs did not affect the pancreatic juice outflow and the lipase output. The protein output was lower when 10.0 mM butyrate or 170.0 mM acetate were infused. The trypsin output decreased for most of the SCFA infusions. The alpha-amylase output decreased for the infusion of 10.0 mM butyrate and tended to decrease for 170.0 mM acetate. The infusions did not change gut hormone level. CONCLUSIONS: Ileal SCFAs might induce an inhibition of pancreatic enzyme secretion under prandial conditions. Ileal SCFAs do not inhibit pancreatic secretion by a hormonal pathway involving the release of peptide YY, motilin, neurotensin, or cholecystokinin.