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.

PREVENT Equation: The Black Sheep among Cardiovascular Risk Scores? A Comparative Agreement Analysis of Nine Prediction Models in High-Risk Lithuanian Women.

Background and Objectives: In the context of female cardiovascular risk categorization, we aimed to assess the inter-model agreement between nine risk prediction models (RPM): the novel Predicting Risk of cardiovascular disease EVENTs (PREVENT) equation, assessing cardiovascular risk using SIGN, the Australian CVD risk score, the Framingham Risk Score for Hard Coronary Heart Disease (FRS-hCHD), the Multi-Ethnic Study of Atherosclerosis risk score, the Pooled Cohort Equation (PCE), the QRISK3 cardiovascular risk calculator, the Reynolds Risk Score, and Systematic Coronary Risk Evaluation-2 (SCORE2). Materials and Methods: A cross-sectional study was conducted on 6527 40-65-year-old women with diagnosed metabolic syndrome from a single tertiary university hospital in Lithuania. Cardiovascular risk was calculated using the nine RPMs, and the results were categorized into high-, intermediate-, and low-risk groups. Inter-model agreement was quantified using Cohen's Kappa coefficients. Results: The study uncovered a significant diversity in risk categorization, with agreement on risk category by all models in only 1.98% of cases. The SCORE2 model primarily classified subjects as high-risk (68.15%), whereas the FRS-hCHD designated the majority as low-risk (94.42%). The range of Cohen's Kappa coefficients (-0.09-0.64) reflects the spectrum of agreement between models. Notably, the PREVENT model demonstrated significant agreement with QRISK3 (κ = 0.55) and PCE (κ = 0.52) but was completely at odds with the SCORE2 (κ = -0.09). Conclusions: Cardiovascular RPM selection plays a pivotal role in influencing clinical decisions and managing patient care. The PREVENT model revealed balanced results, steering clear of the extremes seen in both SCORE2 and FRS-hCHD. The highest concordance was observed between the PREVENT model and both PCE and QRISK3 RPMs. Conversely, the SCORE2 model demonstrated consistently low or negative agreement with other models, highlighting its unique approach to risk categorization. These findings accentuate the need for additional research to assess the predictive accuracy of these models specifically among the Lithuanian female population.

A Novel Adaptive Noise Elimination Algorithm in Long RR Interval Sequences for Heart Rate Variability Analysis.

As heart rate variability (HRV) studies become more and more prevalent in clinical practice, one of the most common and significant causes of errors is associated with distorted RR interval (RRI) data acquisition. The nature of such artifacts can be both mechanical as well as software based. Various currently used noise elimination in RRI sequences methods use filtering algorithms that eliminate artifacts without taking into account the fact that the whole RRI sequence time cannot be shortened or lengthened. Keeping that in mind, we aimed to develop an artifacts elimination algorithm suited to long-term (hours or days) sequences that does not affect the overall structure of the RRI sequence and does not alter the duration of data registration. An original adaptive smart time series step-by-step analysis and statistical verification methods were used. The adaptive algorithm was designed to maximize the reconstruction of the heart-rate structure and is suitable for use, especially in polygraphy. The authors submit the scheme and program for use.

Prevalence of Cardiovascular Risk Factors in Middle-Aged Lithuanian Men Based on Body Mass Index and Waist Circumference Group Results from the 2006-2016 Lithuanian High Cardiovascular Risk Prevention Program.

Background and aims: This study aimed to estimate the prevalence of cardiovascular risk factors in middle-aged Lithuanian men categorized according to body mass index and waist circumference results. Methods and results: The data were from the Lithuanian High Cardiovascular Risk primary prevention program between 2009 and 2016. This community-based cross-sectional study comprised 38,412 men aged 40 to 54 years old. We compared the prevalence of arterial hypertension, dyslipidaemia, diabetes mellitus, smoking, and metabolic syndrome in body mass index (BMI) and waist circumference (WC) groups. Regarding the allometric anthropometrics for WC, A Body Shape Indices (ABSIs) were analyzed with respect to mortality risk and smoking status. The most prevalent risk factor in men was dyslipidaemia, followed by arterial hypertension and smoking (86.96%, 47.94%, and 40.52%, respectively). All risk factors except for smoking were more prevalent in men with overweight or obesity as measured by BMI compared to men with normal weight. Similarly, smoking was the only cardiovascular risk factor that was more prevalent among subjects with normal WC compared to those with increased WC or abdominal obesity. Elevated ABSI, which is associated with higher mortality risk, was more prevalent in smokers. Conclusion: The most prevalent cardiovascular risk factor among middle-aged Lithuanian men was dyslipidaemia, with a surprisingly high prevalence in all BMI and WC groups. Smoking was the only risk factor most prevalent in subjects with low or normal weight according to BMI. It was also more prevalent in the normal WC group compared to the increased WC or abdominal obesity groups, but ABSI values associated with higher mortality were more prevalent among smokers than non-smokers.

Inflammaging and Vascular Function in Metabolic Syndrome: The Role of Hyperuricemia.

Background and Objectives: Early vascular aging determines a more rapid course of age-related arterial changes. It may be induced by a proinflammatory state, caused by hyperuricemia and metabolic syndrome and their interrelationship. However, the impact of serum uric acid (SUA) on early arterial stiffening and vascular function remains uncertain. Materials and Methods: A total of 696 participants (439 women aged 50-65 and 257 men aged 40-55) from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program were enrolled in the study. They underwent anthropometric measurements and laboratory testing along with arterial parameters' evaluation. Quality carotid stiffness (QCS), carotid-radial pulse wave velocity (crPWV), carotid-femoral pulse wave velocity (cfPWV), flow-mediated dilatation (FMD), and carotid intima-media thickness (CIMT) were registered. Results: We found that hyperuricemia was significantly associated with inflammation, registered by high-sensitivity C-reactive protein in both sexes. A very weak but significant association was observed between cfPWV and SUA in men and in women, while, after adjusting for risk factors, it remained significant only in women. A positive, weak, but significant association was also observed for QCS, both right and left in women. No relationship was observed between crPWV, FMD, CIMT, and SUA.

Which Clusters of Metabolic Syndrome Are the Most Associated with Serum Uric Acid?

Background and Objectives: Metabolic syndrome is defined as three or more of five components; therefore, there are 16 possible different clusters of metabolic risk factors that are under one diagnosis of metabolic syndrome. In this study, we evaluated the different clusters of metabolic syndrome (MetS) across serum uric acid (SUA) quartiles and analyzed the association of these clusters with SUA levels, respectively, in both men and women. Materials and Methods: A total of 606 subjects were recruited to a cross-sectional study from the ongoing Lithuanian High Cardiovascular Risk primary prevention program (LitHiR). All of the study subjects were diagnosed with MetS (according to the 2005 National Cholesterol Education Program Adult Treatment Panel III MetS definition). Results: In the middle-aged population of patients with MetS living in Lithuania, a high proportion of hyperuricaemia was detected-35.5% (95% Cl 31.7% to 39.4%). For women possessing all five MetS components, the chances of having hyperuricaemia are 2.807 higher than for women with three risk factors (p < 0.001). However, men do not have a statistically significantly higher chance of having hyperuricaemia, depending on the number of MetS components in our population. Using multivariable models, the statistically significant chance of having hyperuricaemia was observed only in women possessing all five MetS components (OR = 2.386, p < 0.0001), compared to any other of 15 MetS clusters. After adjustment for age and sex, the chance of having hyperuricaemia for individuals with the cluster of all five MetS components, compared to any other of 15 MetS clusters, remained (OR = 1.982, p = 0.001). Also, a lower probability (OR = 0.653, p = 0.039) of having hyperuricaemia was observed for individuals having the combination of abnormal plasma glucose, blood pressure, and waist circumference. Conclusions: Patients with the clustering of all five metabolic syndrome components are at higher risk for having hyperuricaemia than patients with any other combination of MetS clusters. This risk is even higher for women. It could be beneficial for patients presented with all five MetS components to be screened for SUA concentration in the primary CVD prevention program.

Hypertriglyceridemia impact on arterial parameters in patients with metabolic syndrome.

BACKGROUND: The development of metabolic syndrome (MS) augments risk for atherosclerotic cardiovascular disease (CVD), but pathophysiological mechanisms of this relation are still under discussion. Overlapping CVD risk factors make it difficult to assess the importance of individual elements. This study aimed to analyze subclinical atherosclerosis based on arterial structure and function parameters in patients with MS and different triglycerides levels. METHODS: Patients (aged 40-65 years) were divided into two groups: patients with MS and with or without hypertriglyceridemia (hTG). Noninvasive assessment of vascular parameters-aortic augmentation index adjusted for heart rate 75 bpm (AIxHR75), pulse wave velocity (PWV), and common carotid artery intima-media thickness (cIMT) were performed. RESULTS: Carotid-femoral PWV (cfPWV) and carotid-radial PWV (crPWV) were significantly higher in patients with hTG. After adjusting for age, gender, waist circumference, fasting glucose, smoking status, cardiovascular family history and mean arterial pressure, crPWV (OR 1.150; CI 95% 1.04-1.28), cfPWV (OR 1.283; CI 95% 1.14-1.42) and cIMT (OR 1.13; CI 95% 1.02-1.25) were significantly associated with hTG (p < 0.05), while AIxHR75 did not show significant association. CONCLUSION: Increased triglycerides are independently associated with a cfPWV, crPWV, and cIMT and may modify CVD risk in patients with MS.

The Experience, Prerequisites, and the Barriers in Organizing a Specialized Rehabilitation Program for Patients with Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a severe progressive disease, associated with reduced exercise capacity and poor quality of life. Although scientific evidence supports the incorporation of specialized training in the treatment of PH, it is only available in a few countries. OBJECTIVES AND METHODS: This article aims to share the experience of implementing a PH rehabilitation program, to summarize the barriers and prerequisites for launching this service, and to assess its early effect. We retrospectively analyzed our pathway in organizing this program, by singling out essential steps. RESULTS: The preparation phase took about 14 months. Establishing and running of a PH rehabilitation program required dedicated rehabilitation specialists to join the multidisciplinary PH expert team. Team members needed to gain special knowledge on exercise training in severely compromised patients; thus, supervision and education by experienced consultants was crucial. The main eligibility criteria for patients were stable status, optimal medical treatment, and motivation to undergo the training. The first results evaluating the effect of a specialized PH training program in 9 patients are promising. Seven of them improved their functional capacity over the period of 15 weeks. CONCLUSIONS: Despite a number of challenges and barriers, the implementation of a specialized rehabilitation program should be encouraged in a few dedicated PH expert centers per country, who are capable to fulfill all prerequisites and organizational aspects. Local PH experts, supervision by an experienced center, in-patient rehabilitation facilities, dedicated personnel, equipment, and patient motivation are essential.

Long-Term Effects of Renal Artery Denervation.

Background and Objectives: Renal artery denervation (RDN) procedure is a broadly discussed method in the treatment of resistant hypertension. Many studies report short-term (3-12 months) results for blood pressure and arterial stiffness. The primary endpoints were changes in 24 h mean systolic blood pressure (BP) and office systolic BP 48 months after RDN. The secondary endpoints were changes in aortic pulse wave velocity and impact of polypharmacy on these variables. Materials and Methods: Renal artery denervation was performed in 73 patients treated for resistant hypertension; 49 patients remained in final analysis. Patient examination was carried out before the procedure, and subsequently at 3, 6, 12, 24, and 48 months later. Patients' antihypertensive and overall medication regimens were carefully analysed. Results: Mean 24 h arterial blood pressure lowered and was sustained at lower levels for up to 48 months; median (interequartile range-IQR) from 158(23.5)/100(14.2) to 140(26.5)/86(16.2) mmHg. Mean reduction in 24 h ambulatory systolic BP was -11 ± 25 mmHg (95% CI, -20 to -2; p < 0.001), while office systolic BP reduced by -7 ± 23 mmHg (95%CI, -24 to -1; p < 0.02). A significant reduction in median aortic pulse wave velocity 12 months after the procedure (drop from baseline 11.2 [3.15] m/s (95%CI 6.1 to 16.2) to 9.8 [2.1] m/s (95%CI 6.1 to 13.7; p = 0.002)). After 48 months, there was no worsening compared to the baseline level of 10.3 [4.0] m/s (95% CI 6.9 to 17.8) (p > 0.05). The total mean number of antihypertensive drugs remained unchanged: 5.97(±1.1) vs. 5.24 (±1.45). A higher number of pills after 48 months was associated with higher aortic pulse wave velocity (1-5 pill group: 8.1 ± 1.6 m/s; 6-10 pill group: 10.9 ± 1.8 m/s; >11 pill group: 15.1 ± 2.6 m/s) (p = 0.003). Conclusions: Antihypertensive effect after renal denervation lasts up to 48 months with no worsening of arterial stiffness compared to baseline. In our study, polypharmacy was associated with increased arterial stiffness 48 months after the procedure.

The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure.

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

Incidence of cardiovascular events in patients with stabilized coronary heart disease: the EUROASPIRE IV follow-up study.

The EUROASPIRE surveys (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) demonstrated that most European coronary patients fail to achieve lifestyle, risk factor and therapeutic targets. Here we report on the 2-year incidence of hard cardiovascular (CV) endpoints in the EUROASPIRE IV cohort. EUROASPIRE IV (2012-2013) was a large cross-sectional study undertaken at 78 centres from selected geographical areas in 24 European countries. Patients were interviewed and examined at least 6 months following hospitalization for a coronary event or procedure. Fatal and non-fatal CV events occurring at least 1 year after this baseline screening were registered. The primary outcome in our analyses was the incidence of CV death or non-fatal myocardial infarction, stroke or heart failure. Cox regression models, stratified for country, were fitted to relate baseline characteristics to outcome. Our analyses included 7471 predominantly male patients. Overall, 222 deaths were registered of whom 58% were cardiovascular. The incidence of the primary outcome was 42 per 1000 person-years. Comorbidities were strongly and significantly associated with the primary outcome (multivariately adjusted hazard ratio HR, 95% confidence interval): severe chronic kidney disease (HR 2.36, 1.44-3.85), uncontrolled diabetes (HR 1.89, 1.50-2.38), resting heart rate ≥ 75 bpm (HR 1.74, 1.30-2.32), history of stroke (HR 1.70, 1.27-2.29), peripheral artery disease (HR 1.48, 1.09-2.01), history of heart failure (HR 1.47, 1.08-2.01) and history of acute myocardial infarction (HR 1.27, 1.05-1.53). Low education and feelings of depression were significantly associated with increased risk. Lifestyle factors such as persistent smoking, insufficient physical activity and central obesity were not significantly related to adverse outcome. Blood pressure and LDL-C levels appeared to be unrelated to cardiovascular events irrespective of treatment. In patients with stabilized CHD, comorbid conditions that may reflect the ubiquitous nature of atherosclerosis, dominate lifestyle-related and other modifiable risk factors in terms of prognosis, at least over a 2-year follow-up period.

Lower than average HDL cholesterol efflux capacity in Lithuanian population.

BACKGROUND: The aim of our study was to evaluate high-density lipoprotein cholesterol (HDL-C) efflux capacity in healthy controls and patients with severe dyslipidemia. Evaluation of HDL function may be beneficial for better understanding of cardiovascular diseases, as well as for taking actions to minimize residual cardiovascular risk. METHODS: During 2016-2017 a total of 93 participants - 48 (51.6%) women and 45 (48.4%) men - were included in this cross-sectional study. Data of 45 (48.4%) participants with severe dyslipidemia (SD) and 48 (51.6%) controls without dyslipidemia was used for statistical analysis. Total lipid panel, concentration of lipoprotein (a) and apolipoproteins were measured, data about cardiovascular risk factors were collected and detailed evaluation of HDL-C quality was performed for all patients. RESULTS: Increased HDL-C concentration was associated with higher ApoA1 (r = 0.866 in controls, r = 0.63 in SD group), ApoA2 (r = 0.41 in controls, r = 0.418 in SD group) and LDL-C concentrations (r = - 0.412 in SD group), lower ApoE (r = - 0.314 in SD group) and TG concentrations (r = - 0.38 in controls, r = - 0.608 in SD group), lower ApoB/ApoA1 ratio (r = - 0.567 in control group), below average HDL-C efflux capacity (r = - 0.335 in SD group), lower BMI (r = - 0.327 in controls, r = - 0.531 in SD group) and abdominal circumference (r = - 0.309 in women with SD). Below-average HDL-C efflux capacity was found in 67.7% (N = 63) of participants. It was more often found among patients with normal weight or BMI 30-31 kg/m2. HDL-C efflux capacity was inversely associated with HDL-C concentration (r = - 0.228). CONCLUSION: Abnormal HDL function may be associated with residual cardiovascular risk in Lithuanian population.

The effect of cardiac shock wave therapy on myocardial function and perfusion in the randomized, triple-blind, sham-procedure controlled study.

BACKGROUND: Recent triple-blind sham procedure-controlled study revealed neutral effects of the cardiac shock wave therapy (CSWT) on exercise tolerance and symptoms in patients with stable angina. Current data about the effects of CSWT on global and regional myocardial contractility and perfusion is limited. Hereby we report the results of an imaging sub-study that evaluated the capacity of CSWT to ameliorate myocardial ischemia induced during dobutamine stress echocardiography (DSE) and cardiac single photon emission computed tomography (SPECT). METHODS: Prospective, randomized, triple-blind, sham procedure-controlled study enrolled 72 adult subjects who complied with defined inclusion criteria. The subjects were assigned to the OMT + CSWT and the OMT + sham procedure study groups with 1:1 ratio. Application of the CSWT covered all segments of the left ventricle. Imaging ischemia tests were performed in 59 study patients: DSE and SPECT before the CSWT treatment and after 6 months, with DSE carried out additionally at 3 months after randomization. Co-primary endpoints of the study were: change in wall motion score index (WMSI), representing the stress-induced impairment of regional myocardial function, and change in summed difference score (SDS), representing the amount of perfusion defect. RESULTS: OMT + CSWT and OMT + sham procedure study groups included 30 and 29 patients, respectively. Regional myocardial contractility during DSE significantly improved at 3 months follow-up in OMT + CSWT group compared to baseline as shown by WMSI at stress (1.4 ± 0.4 vs 1.6 ± 0.4, p = 0.001), but not in OMT + sham procedure group (1.5 ± 0.3 vs 1.6 ± 0.4, p = 0.136). The difference in stress DSE results between both study groups disappeared after 6 months. SPECT results demonstrated a significant reduction of inducible ischemia in OMT + CSWT group compared to OMT + sham procedure group at 6 months follow-up (SDS dropped from 5.4 ± 3.7 to 3.6 ± 3.8 vs 6.4 ± 5.9 to 6.2 ± 5 respectively, p = 0.034). CONCLUSIONS: Cardiac shock wave treatment showed the ability to reduce stress-induced myocardial ischemia, as assessed by wall motion abnormalities and perfusion defects, compared to sham procedure. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02339454 ). The trial was registered retrospectively on 12 January 2015.

Is the coronary artery calcium score the first-line tool for investigating patients with severe hypercholesterolemia?

BACKGROUND: Coronary artery calcium (CAC) is known as a reliable tool for estimating risk of myocardial infarction, coronary death, all-cause mortality and is even used to evaluate suitable asymptomatic patients. We therefore aimed to evaluate whether CAC scoring can be applied in the algorithm for clinical examination of patients with severe hypercholesterolemia (SH). METHODS: During the period of 2016-2017 a total of 213 asymptomatic adults, underwent computed tomography angiography to evaluate their CAC scoring. The sample consisted of 110 patients with SH and 103 age and sex matched controls without dyslipidemia and established cardiovascular disease. RESULTS: In total there were 79 (37.2%) subjects with elevated (≥25th) CAC percentiles. Out of them 47 (59.5%) had SH and 32 (40.5%) did not. CAC score did not differ between groups (SH (+) 140.30 ± 185.72 vs SH (-) 87.84 ± 140.65, p = 0.146), however there was a comparable difference in how the participants of these groups distributed among different percentile groups (p = 0.044). Gender, blood pressure, tabaco use, physical activity, family history of coronary artery disease and diabetes mellitus were not associated with CAC score (p > 0.05). There were no significant correlations between biochemical parameters and CAC percentiles except for increase in lipoprotein(a) (p = 0.038). Achilles tendon pathology, visceral obesity, body mass index and increased waist-hip ratio were not associated with CAC percentiles either (p > 0.05). CONCLUSIONS: CAC score is not associated with presence of SH. CAC score is not an appropriate diagnostic tool in the algorithm for clinical examination of patients with SH. Further larger studies are needed to support our findings.

Association of aortic stiffness, carotid intima-media thickness and endothelial function with cardiovascular events in metabolic syndrome subjects.

PURPOSE: The objective of this study was to assess predictive value of various arterial markers for cardiovascular (CV) events in patients with metabolic syndrome (MetS). MATERIALS AND METHODS: A longitudinal study with the follow-up period of 3.9 ± 1.7 years investigated 2728 middle-aged (53.9 ± 6.2 years old, 63% women) MetS subjects without overt CV disease. The study cohort was comprised of the participants of the Lithuanian High Cardiovascular Risk primary prevention program. The baseline assessment included the evaluation of brachial flow-mediated dilatation (FMD), carotid intima-media thickness (cIMT), carotid stiffness index, aortic pulse wave velocity (aPWV), aortic augmentation index (AIx), and cardio-ankle vascular index). The data on the cardiovascular outcome (fatal or non-fatal myocardial infarction or stroke) was collected by using the databases of the two major national registries. RESULTS: Over the follow-up period, 83 (3%) patients had at least one cardiovascular event. In a univariate analysis, occurrence of CV events was associated with the following parameters: higher mean blood pressure, aPWV, AIx and cIMT, and lower FMD (all p < .05). In Cox proportional hazard regression analysis, the occurrence of CV event was associated with an increase in aPWV (HR 1.29, 95% CI 1.04-1.60, p = .019), AIx (HR 1.53, 95% CI 1.16-2.02, p = .003), and cIMT (HR 1.31, 95% CI 1.14-1.50, p < .001), and with the decrease in FMD (HR 0.83, 95% CI 0.71-0.97, p = .016) even after the adjustment for age, gender, and common cardiometabolic risk factors. In a two-level survival trees analysis, we established that patients with cIMT > 794 mcm had higher CV risk (p < .001) and their prognosis was further compromised by aPWV > 11.1 m/s (p = .023). Meanwhile, in patients with cIMT ≤ 794mcm, the FMD cut-off point of 6.5% further stratified the risk (p = .003). CONCLUSIONS: In our prospective study, CV risk in the middle-aged patients with MetS was associated with an increase in cIMT and aPWV, and with a decrease in FMD.

A High Prevalence of Intracranial Stenosis in Patients with Coronary Artery Disease and the Diagnostic Value of Transcranial Duplex Sonography.

BACKGROUND: According to the data from the population-based Rotterdam study, intracranial carotid artery calcification detected by computed tomography is very common and contributed to 75% of all strokes. The aim of the present study was to estimate the prevalence of intracranial stenosis (IS) using noninvasive transcranial color-coded duplex sonography (TCCS) in neurologically asymptomatic patients with coronary artery disease (CAD). METHODS: Three hundred and eighty-nine patients with angiographically-confirmed, severe CAD were included prospectively. All of them were examined using extracranial and TCCS. RESULTS: Out of 389 patients (age 66.7 ± 9.2, 39-88), 237 (61%) were diagnosed with 3 vessels disease and 152 patients (39%) with left stem disease with/without 3 vessels damage. Transcranial sonography revealed at least 1 IS in 63.6% of echo positive patients (220/346). IS was found in 127 (61.4%) patients with 3 vessels disease, 20 patients (58.8%) with isolated left stem disease, and 73 patients (69.5%) with 3 vessels and left stem disease (P = .305). In the case of significant (≥50%) extracranial internal carotid artery stenosis, intracranial stenosis were detected in 84.8% (50 of 59), in the case of mild (<50%) stenosis, in 59.2% (170 of 287), P < .001. CONCLUSIONS: It was found that two thirds of patients with advanced CAD have a silent IS. TCCS is a reliable method for the evaluation of intracranial atherosclerosis in such patients in order to gain useful information about cerebrovascular disease as a risk factor for stroke.

Trends in Cigarette Smoking among Middle-Aged Lithuanian Subjects Participating in the Primary Prevention Program between 2009 and 2016.

Background and Objectives: The aim of the study was to evaluate trends in smoking among middle-aged men and women based on the data from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program between 2009 and 2016. Materials and Methods: A community-based cross-sectional study comprised 92373 Lithuanian adults (41.6% men and 58.4% women). We compared the prevalence of smoking, smoking cessation activity and smoking intensity by gender and age groups. Results: There was a statistically significant upward trend in the number of smoking subjects (average annual percent change (AAPC) 2.99%, p < 0.001). The number of smoking male subjects remained much higher than the number of smoking female subjects during the 2009-2016 period. The study showed a significant increase in the percentage of smoking quitters in the whole group (AAPC 7.22%, p < 0.001) and among men and women separately. There was no significant change in smoking intensity in groups of male and female smokers separately. Conclusions: The analysis showed that the prevalence of smoking in Lithuania is still increasing due to women smoking despite all the governmental tobacco control efforts to reduce it.

Daily Heart Rate Variability Indices in Subjects with and Without Metabolic Syndrome Before and After the Elimination of the Influence of Day-Time Physical Activity.

Background and Objectives: The available research shows conflicting data on the heart rate variability (HRV) in metabolic syndrome (MetS) subjects. The discrepancy suggests a methodical shortcoming: due to the influence of physical activity, the standard measuring of HRV at rest is not comparable with HRV assessment based on 24h Holter monitoring, which is preferred because of its comprehensiveness. To obtain a more reliable measure and to clarify to what extent HRV is altered in MetS, we assessed a 24h HRV before and after the elimination of the influence of physical activity. Materials and Methods: We investigated 69 metabolic syndrome (MetS) and 37 control subjects, aged 50-55. In all subjects, 24h monitoring of electrocardiogram, blood pressure, and actigraphy profiles were conducted. To eliminate the influence of day-time physical activity on RR intervals (RRI), a linear polynomial autoregressive model with exogenous terms (ARX) was used. Standard spectral RRI analysis was performed. Results: Subjects with MetS had blunted HRV; the diurnal SDNN index was reliably lower in the MetS group than in control subjects. The elimination of the influence of physical activity did not reveal a significant HRV change in long-term indices (SDNN, SDANN, and SD2), whilst adjacent RRI values (RMSSD, pNN50, and SD1) and SDNN index significantly increased (p < 0.001). An increase in the latter indices highlighted the HRV difference between the MetS and control groups; a significant (p < 0.001) decrease of all short-term HRV variables was found in the MetS group (p < 0.01), and low-frequency spectral components were less pronounced in the MetS group. Conclusion: The application of a polynomial autoregressive model in 24h HRV assessment allowed for the exclusion of the influence of physical activity and revealed that MetS is associated with blunted HRV, which reflects mitigated parasympathetic tone.

Cardiovascular risk assessment of dyslipidemic middle-aged adults without overt cardiovascular disease over the period of 2009-2016 in Lithuania.

BACKGROUND: Cardiovascular mortality in Lithuania is extremely high and abnormal lipid levels are very common among Lithuanian adults. Dyslipidemia is one of the main independent risk factors for cardiovascular diseases (CVD) leading to high absolute CVD risk. The aim of this study was to assess CVD risk in dyslipidemic middle-aged subjects. METHODS: During the period of 2009-2016 a total of 92,373 people (58.4% women and 41.6% men) were evaluated. This study included men aged 40-54 and women aged 50-64 without overt CVD. RESULTS: Any type of dyslipidemia was present in 89.7% of all study population. 7.5% of dyslipidemic patients did not have any other conventional risk factors. Three and more risk factors were detected in 60.1% of dyslipidemic subjects. All analyzed risk factors, except smoking, were more common in dyslipidemic adults compared to subjects without dyslipidemia: arterial hypertension (55.8% vs. 43.3%, p < 0.001), diabetes (11.1% vs. 7.3%, p < 0.001), abdominal obesity (45.3% vs. 30.2%, p < 0.001), BMI ≥30 kg/m2 (35.8% vs. 23.7%, p < 0.001), metabolic syndrome (34.0% vs. 9.2%, p < 0.001), family history of coronary heart disease (26.3% vs. 23.1%, p < 0.001), unbalanced diet (62.5% vs. 52.9%, p < 0.001) and insufficient physical activity (52.0% vs. 44.2%, p < 0.001). The prevalence of all evaluated risk factors, except smoking, increased with age. Average SCORE index was 1.87 in all study population, while dyslipidemic subjects had higher SCORE compared to control group (1.95 vs 1.20, p < 0.001). CONCLUSIONS: Almost two thirds of dyslipidemic middle-aged Lithuanian adults without overt cardiovascular disease had three or more other CVD risk factors, which synergistically increase absolute risk of CVD. The average 10-year risk of CVD death in patients with dyslipidemia was 1.95%. The importance of managing dyslipidemia as well as other risk factors in order to reduce burden of cardiovascular disease in Lithuania is evident.

Cardiovascular risk profile of patients with atherogenic dyslipidemia in middle age Lithuanian population.

BACKGROUND: Atherogenic dyslipidemia (AD) is a blood serum lipid profile abnormality characterized by elevation of triglycerides and reduced levels of high density lipoprotein cholesterol (HDL-C). It is associated with residual cardiovascular risk. This study evaluated and compared the risk profiles of patients with hypertriglyceridemia, low-HDL-C levels or AD, in order to understand, which lipid profile is associated with greater risk. METHODS: During the period of 2009-2016 a population of 92,373 Lithuanian adults (men 40-54 years old and women 50-64 years old) without overt cardiovascular disease were analyzed. Data of 25,746 patients (68.6% women and 31.4% men) with hypertriglyceridemia and/or low HDL-C low levels were collected and used for further statistical analysis. RESULTS: Participants with AD tend to have more unfavorable risk profile than participants with hypertriglyceridemia or low-HDL-C. AD tends to cluster with other atherogenic risk factors, such as arterial hypertension [odds ratio (OR) 1.96, 95% confidence intervals (CI) 1.87-2.01], smoking [OR 1.20, 95% CI 1.14-1.27], diabetes mellitus [OR 2.74, 95% CI 2.58-2.90], obesity [OR 2.92, 95% CI 2.78-3.10], metabolic syndrome [OR 22.27, 95% CI 20.69-23.97], unbalanced diet [OR 1,59, 95% CI 1.51-1.68], low physical activity [OR 1.80, 95% CI 1.71-1,89], CHD history in first degree relatives [OR 1.18, 95% CI 1.12-1.25] and total number of risk factors [OR 1.47, 95% CI 1.38-1.57]. CONCLUSION: AD is associated with more unfavorable cardiovascular risk profile than hypertriglyceridemia or low-HDL cholesterol levels. Once identified AD should require additional medical attention since it is an important factor of residual cardiovascular risk.