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.

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.

Navigating the Landscape of Cardiovascular Risk Scores: A Comparative Analysis of Eight Risk Prediction Models in a High-Risk Cohort in Lithuania.

Background: Numerous cardiovascular risk prediction models (RPM) have been developed, however, agreement studies between these models are scarce. We aimed to assess the inter-model agreement between eight RPMs: assessing cardiovascular risk using SIGN, the Australian CVD risk score (AusCVDRisk), the Framingham Risk Score for Hard Coronary Heart Disease, 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). Methods: A cross-sectional study was conducted on 11,174 40-65-year-old individuals with diagnosed metabolic syndrome from a single tertiary university hospital in Lithuania. Cardiovascular risk was calculated using the eight 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 revealed significant heterogeneity in risk categorizations with only 1.49% of cases where all models agree on the risk category. SCORE2 predominantly categorized participants as high-risk (67.39%), while the PCE identified the majority as low-risk (62.03%). Cohen's Kappa coefficients ranged from -0.09 to 0.64, indicating varying degrees of inter-model agreement. Conclusions: The choice of RPM can substantially influence clinical decision-making and patient management. The PCE and AusCVDRisk models exhibited the highest degree of agreement while the SCORE2 model consistently exhibited low agreement with other models.

Effect of Alcohol Consumption Habits on Early Arterial Aging in Subjects with Metabolic Syndrome and Elevated Serum Uric Acid.

BACKGROUND: Hyperuricemia is perceived as one of the risk factors for developing and progressing cardiovascular disease and metabolic syndrome through various pathological mechanisms. Endogenous synthesis and exogenous factors such as diet and beverages consumed play a major role in determining serum uric acid (sUA) levels. The aim of this study was to evaluate the effect of alcohol consumption on early arterial aging in middle-aged patients with metabolic syndrome (MetS) and hyperuricemia. MATERIALS AND METHODS: This study included 661 middle-aged subjects (241 men and 420 women) from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program. Characteristics of subjects such as blood pressure, laboratory testing, and the specialized nutrition profile questionnaire were evaluated. As an early marker of arterial stiffness, carotid-femoral pulse wave velocity (cfPWV) was assessed using a non-invasive applanation tonometry technique. RESULTS: Hyperuricemia was present in 29% of men and 34% of women. Hyperuricemic men reported 1.6 times higher rates of alcohol drinking compared to men with normal sUA levels. After analyzing the correlation between alcohol consumption and cfPWV, no statistically significant relationships were found at a significance level of α = 0.05 but lowering the significance level to 0.06 revealed significant associations in men with normal sUA (ε2ordinal = 0.05, p = 0.06) and in women with increased sUA levels (ε2ordinal = 0.05, p = 0.08). Regression analysis showed that hyperuricemic men, consuming more than one unit of alcohol per week, had a significant impact on increasing cfPWV, while men with normal sUA levels, abstaining from alcohol entirely, resulted in a statistically significant decrease in cfPWV. Our results showed statistically significant relationships only among a group of men, although the women in the hyperuricemic group had a statistically higher cfPWV than women with normal sUA levels. CONCLUSIONS: Drinking alcohol is associated with increased arterial stiffness among hyperuricemic middle-aged men with MetS.

Ambulatory and successive home-based heart rate targeted aerobic training improves arterial parameters: a follow-up study in people with metabolic syndrome.

BACKGROUND: Studies demonstrated that outpatient aerobic exercise programs (aEP) can significantly decrease aortic stiffness in people with metabolic syndrome (MetS). There is some limited data that remotely supervised home-based aEP can also improve arterial stiffness in this population. We aimed to evaluate the changes in the arterial wall parameters after the 2-month ambulatory supervised aEP followed by the 6-month home-based aEP with and without targeting of heart rate (HR) by electrocardiogram (ECG) in people with MetS. METHODS: In this prospective study (ClinicalTrials.gov identifier: NCT05592704) 132 MetS subjects (mean age 52.44 ± 6.26 years, 54.55% female) were evaluated. At first, all subjects participated in the 2-month ambulatory supervised aEP, which consisted of 40 individual aerobic training sessions on a cycle ergometer 5 times/week for 40 min and received the recommendations for home-based training. Then the study (n = 66) and the control (n = 66) groups participated in the 6-month home-based aEP, but only the study group subjects targeted their HR using ECG monitor connected to the smartphone during workouts. Arterial stiffness parameters and carotid artery intima-media thickness (cIMT) were evaluated in all participants at baseline and after 8 months. RESULTS: After 8 months, carotid-femoral pulse wave velocity (c-f PWV) significantly reduced in both groups (-12.22% in the study group vs. -7.85% in the control group, all p < .001) without a significant between-group difference (p = 0.144). A significant improvement of carotid-radial pulse wave velocity (c-r PWV) was observed only in the study group (-11.37%, p < .001, d = -0.671) with significant between-group difference (p < .001). The reduction of c-r PWV after 8 months of aEP occurred when c-r PWV at baseline was in the 2nd quartile (>7.90 m/s). A significant decrease of 3.32% in cIMT was present only in the study group (p = .032, d = -0.288). CONCLUSIONS: The combination of 2-month ambulatory supervised aEP and successive 6-month home-based aEP targeted by HR monitoring using ECG improved arterial properties in MetS subjects more than the same combination without HR targeting, leading to the greater reduction of c-r PWV and cIMT.

The combination of 2-month ambulatory supervised aEP and successive 6-month home-based aEP targeted by HR monitoring using ECG improved arterial properties in MetS subjects more than the same combination without HR targeting, leading to the greater reduction of c-r PWV and cIMT.This study foregrounds the importance of home-based training with HR targeting using ECG in people with MetS.

Type 2 Myocardial Infarction and Long-Term Mortality Risk Factors: A Retrospective Cohort Study.

INTRODUCTION: In-hospital risk factors for type 1 myocardial infarction (MI) have been extensively investigated, but risk factors for type 2 MI are still emerging. Moreover, type 2 MI remains an underdiagnosed and under-researched condition. Our aim was to assess survival rates after type 2 MI and to analyze the risk factors for patient prognosis after hospitalization. METHODS: We conducted a retrospective database analysis of patients with MI diagnosis who were treated in Vilnius University Hospital Santaros Klinikos. A total of 6495 patients with the diagnosis of MI were screened. The primary study endpoint was long-term all-cause mortality. The predictive value of laboratory tests was estimated including blood hemoglobin, D dimer, creatinine, brain natriuretic peptide (BNP), C-reactive protein (CRP), and troponin levels. RESULTS: Out of all the patients diagnosed with MI there were 129 cases of type 2 MI (1.98%). Death rate almost doubled from 19.4% at 6 months to 36.4% after 2 years of follow-up. Higher age and impaired kidney function were risk factors for death both during hospitalization and after 2 years of follow-up. Lower hemoglobin (116.6 vs. 98.9 g/L), higher creatinine (90 vs. 161.9 µmol/L), higher CRP (31.4 vs. 63.3 mg/l), BNP (707.9 vs. 2999.3 ng/L), and lower left ventricle ejection fraction were all predictors of worse survival after 2 years of follow-up. Preventive medication during hospitalization can decrease the mortality risk: angiotensin-converting enzyme inhibitor (ACEi) (HR 0.485, 95% CI 0.286-0.820) and statins (HR 0.549, 95% CI 0.335-0.900). No significant influence was found for beta blockers (HR 0.662, 95% CI 0.371-1.181) or aspirin (HR 0.901, 95% CI 0.527-1.539). CONCLUSIONS: There is significant underdiagnosis of type 2 MI (1.98% out of all MIs). If the patient is prescribed a preventive medication like ACEi or statins, the mortality risk is lower. Increased awareness of elevation of laboratory results could help to improve the treatment of these patients and identify the most vulnerable groups.

The association of catestatin and endocan with the effects of cardiac shock wave therapy: Biomarker sub-study of the randomized, sham procedure-controlled trial.

Introduction: Cardiac shock-wave therapy (CSWT) is a non-invasive regenerative treatment method based on low-frequency ultrasound waves, which stimulate angiogenesis. Current data about the effects of revascularization procedures on angiogenesis biomarkers is limited. Recently, an association of catestatin and endocan with coronary collateral development was shown in several trials. In this study, we aimed to evaluate the impact of CSWT on the dynamics of catestatin and endocan levels and to assess their correlation with parameters of myocardial perfusion and function. Methods: Prospective, randomized, triple-blind, sham procedure-controlled study enrolled 72 adult subjects who complied with defined inclusion criteria (NCT02339454). We measured biomarkers in 48 patients with stable angina (24 patients of CSWT group, 24 patients of sham-procedure group). Additionally, patients were divided into responders and non-responders according to improvement in myocardial perfusion and/or contractility assessed by myocardial scintigraphy and dobutamine echocardiography (30 and 13 patients, respectively). The blood samples were collected at baseline, after the last treatment procedure (9th treatment week) and at 6-month follow-up to evaluate biomarkers concentration and stored at -80° until analysis. Serum catestatin and endocan levels were determined by commercially available ELISA kits. Results: Serum catestatin concentration significantly increased in all patients. While endocan levels significantly decreased in the responders sub-group. The increase in catestatin levels at 9th week and 6 months was positively associated with improvement in summed difference score (rho = 0.356, p = 0.028) and wall motion score, WMS (rho = 0.397, p = 0.009) at 6 months in the whole study population. Meanwhile, the decrease in endocan levels over 6 months was positively correlated with improvement in WMS at 3- and 6- months (r = 0.378, p = 0.015 and r = 0.311, p = 0.045, respectively). ROC analysis revealed that a change at 6 months in catestatin and endocan levels significantly predicted improvement in myocardial perfusion and contractile function with 68.9% sensitivity and 75.0% specificity (p = 0.039) and 51.7% sensitivity, and 91.7% specificity (p = 0.017), respectively. Baseline endocan concentration and its change at 6 months predicted response to CSWT with 68.8% sensitivity and 83.3% specificity (p = 0.039) and 81.3% sensitivity and 100% specificity (p < 0.0001), respectively. Conclusion: This study demonstrates the association of increase in catestatin and decrease in endocan levels with the improvement of myocardial perfusion and contractile function. The potential predictive value of catestatin and endocan dynamics for the response to regenerative therapy is shown.

Prevalence of cardiovascular risk factors in middle-aged Lithuanian women in different body mass index and waist circumference groups.

BACKGROUND AND AIMS: The aim of this study was to evaluate the prevalence of cardiovascular risk factors in middle-aged Lithuanian women in different body mass index and waist circumference groups. METHODS AND RESULTS: Data selected from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program between 2009 and 2016. This community-based cross-sectional study comprised 53,961 women aged 50-64 years old. We compared the prevalence of arterial hypertension, dyslipidaemia, diabetes mellitus, smoking, and metabolic syndrome in different body mass index (BMI) and waist circumference (WC) groups. The most prevalent cardiometabolic risk factor was dyslipidaemia (91.71%, n = 49,488). The prevalence of arterial hypertension, dyslipidaemia, diabetes mellitus, and metabolic syndrome was greater in those with higher-than-normal BMI and WC. Smoking was the most prevalent in women with low BMI and normal WC (24.00% and 13.17% respectively). CONCLUSION: The analysis showed that all risk factors, except smoking, were significantly more prevalent in women with higher-than-normal BMI and with increased WC or abdominal obesity. The prevalence of dyslipidaemia was surprisingly high in all BMI and WC groups. Obesity measured by WC was more strongly associated with an adverse metabolic profile.

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.

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.

Clusters of risk factors in metabolic syndrome and their influence on central blood pressure in a global study.

The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified "risky clusters" of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management.

Chest pain in the emergency department: From score to core-A prospective clinical study.

High-sensitivity troponin assay brought new challenges as we detect elevated concentration in many other diseases, and it became difficult to distinguish the real cause of this elevation. In this notion, diagnosis of acute coronary syndrome (ACS) remains a challenge in emergency department (ED). We aim to examine different approaches for rule-in and rule-out of ACS using risk scores, copeptin, and coronary computed tomography angiography (CCTA). A prospective observational study was designed to evaluate chest pain patients. Consecutive adult patients admitted to the ED with a chief complaint of chest pain due to any cause were included. All patients were followed-up for 6 months after discharge for major adverse cardiovascular events and readmissions. Admission data, ED processes, and diagnoses were analyzed. One hundred forty-six patients were included, average age was 63 ± 13.4 years, and 95 (65.1%) were male. Global Registry of Acute Coronary Events (GRACE) and History, ECG, Age, Risk factors, Troponin (HEART) scores showed good prognostic abilities, but HEART combination with copeptin improves diagnoses of myocardial infarction (area under the curve [AUC] 0.764 vs AUC 0.864 P = .0008). Patients with elevated copeptin were older, had higher risk scores, and were more likely to be admitted to hospital and diagnosed with ACS in ED. For copeptin, AUC was 0.715 (95% confidence interval 0.629-0.803), and for combination with troponin, AUC of 0.770 (0.703-0.855) did not improve rule-in of myocardial infarction. High-sensitivity troponin I assay alongside prior stroke, history of carotid stenosis, dyslipidemia, use of diuretics, and electrocardiogram changes (left bundle branch block or ST depression) are good predictors of myocardial infarction (χ² = 52.29, AUC = 0.875 [0.813-0.937], P < .001). The regression analysis showed that combination of copeptin and CCTA without significant stenosis can be used for ACS rule-out (χ² = 26.36, P < .001, AUC = 0.772 [0.681-0.863], negative predictive value of 96.25%). For rule-in of ACS, practitioner should consider not only scores for risk stratification but carefully analyze medical history and nonspecific electrocardiogram changes and even with normal troponin results, we strongly suggest thorough evaluation in chest pain unit. For rule-out of ACS combination of copeptin and CCTA holds great potential.

Changes in health-related quality of life, motivation for physical activity, and the levels of anxiety and depression after individualized aerobic training in subjects with metabolic syndrome.

OBJECTIVE: Numerous studies associate metabolic syndrome (MetS) with poor life quality, depression, and anxiety. Aerobic exercise training has proven its value in promoting health among subjects with MetS. We aimed to evaluate the changes in health-related quality of life (HRQOL), motivation for physical activity, and the levels of anxiety and depression in subjects with MetS after individualized aerobic training. METHODS: A total of 140 subjects with MetS (53.2 ± 6.8 years, 55% female) were analyzed after the random assignment to the intervention (n = 84) or the control group (n = 56). Only the intervention group participated in the 8-week HR targeted aerobic training program, which consisted of exercises on a cycle ergometer for 30­40 min/day, 5 days/week. In all study participants HRQOL, motivation for physical activity, anxiety and depression levels were evaluated by the Medical Outcomes Study 36-Item Short-Form Health Survey, the Exercise Motivations Inventory-2, and the Hospital Anxiety and Depression scale before and after 8 weeks. RESULTS: After 8 weeks, self-reported physical functioning significantly increased only in the intervention group (p = 0.01). The scores of mental health-summary and role limitations due to emotional problems also improved in subjects with MetS, who participated in the aerobic training program (p < 0.001, p = 0.009, respectively). The scores for social engagement motive, enjoyment and revitalization motive, and fitness motive to exercise increased (p = 0.003, p < 0.001, p = 0.023, respectively), whereas the level of depression reduced only in the intervention group (p = 0.021). CONCLUSIONS: The 8-week individualized aerobic training had a positive effect on HRQOL, motivation for physical activity, and the level of depression in subjects with MetS.

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.

Biologically Active Adrenomedullin (bio-ADM) is of Potential Value in Identifying Congestion and Selecting Patients for Neurohormonal Blockade in Acute Dyspnea.

PURPOSE: This study was designed to evaluate the role of biologically active adrenomedullin (bio-ADM) in congestion assessment and risk stratification in acute dyspnea. METHODS: This is a sub-analysis of the Lithuanian Echocardiography Study of Dyspnea in Acute Settings. Congestion was assessed by means of clinical (peripheral edema, rales) and sonographic (estimated right atrial pressure) parameters. Ninety-day mortality was chosen for outcome analysis. RESULTS: There were 1188 patients included. Bio-ADM concentration was higher in patients with peripheral edema at admission (48.2 [28.2-92.6] vs 35.4 [20.9-59.2] ng/L, P < .001). There was a stepwise increase in bio-ADM concentration with increasing prevalence of rales: 29.8 [18.8-51.1], 38.5 [27.5-67.1], and 51.1 [33.1-103.2] ng/L in patients with no rales, rales covering less than one-half, and greater than or equal to one-half of the pulmonary area, respectively (P < 0.001). Bio-ADM concentration demonstrated gradual elevation in patients with normal, moderately, and severely increased estimated right atrial pressure: 25.1 [17.6-42.4] ng/L, 36.1 [23.1-50.2], and 47.1 [30.7-86.7] ng/L, respectively (P < .05). Patients with bio-ADM concentration >35.5 ng/L were at more than twofold increased risk of dying (P < .001). Survival in those with high bio-ADM was significantly modified by neurohormonal blockade at admission (P < .05), especially if NT-proBNP levels were lower than the median (P = .002 for interaction). CONCLUSION: Bio-ADM reflects the presence and the degree of pulmonary, peripheral, and intravascular volume overload and is strongly related to 90-day mortality in acute dyspnea. Patients with high bio-ADM levels demonstrated survival benefit from neurohormonal blockade.

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.

Randomized Pilot Trial on Optimal Treatment Strategy, Myocardial Changes, and Prognosis of Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains an unresolved challenge. Many different diagnostic approaches are often required to diagnose, confirm, and evaluate MINOCA. The prevalence can be as high as 13% of all acute myocardial infarction patients, indicating that this condition is not rare. At this time, there have been no completed randomized clinical trials involving MINOCA patients, and a better understanding of the mechanisms and management of these patients is important. This exploratory analysis seeks to find possible etiologic factors, the value of novel biomarkers, and the effect of different treatment strategies in patients with MINOCA. METHODS: This prospective randomized pilot trial will include 150 patients with MINOCA. A thorough clinical, laboratory, and imaging evaluation will be performed, including novel biomarkers and modern imaging techniques (heart magnetic resonance imaging and noninvasive testing). The duration of the enrollment is 18 months, and duration of the follow-up is 12 months from the enrollment of the first patient. RESULTS: The trial is registered under www.clinicaltrials.gov: NCT04538924. The study is currently recruiting participants. CONCLUSIONS: Because MINOCA is not a benign disease, the results of the current investigation could inform future diagnostic and therapeutic strategies and enhance the understanding of MINOCA patients.

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.

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.

Readmission following both cardiac and non-cardiac acute dyspnoea is associated with a striking risk of death.

AIMS: Readmission and mortality are the most common and often combined endpoints in acute heart failure (AHF) trials, but an association between these two outcomes is poorly investigated. The aim of this study was to determine whether unplanned readmission is associated with a greater subsequent risk of death in patients with acute dyspnoea due to cardiac and non-cardiac causes. METHODS AND RESULTS: Derivation cohort (1371 patients from the LEDA study) and validation cohort (1986 patients from the BASEL V study) included acute dyspnoea patients admitted to the emergency department. Cox regression analysis was used to determine the association of 6 month readmission and the risk of 1 year all-cause mortality in AHF and non-AHF patients and those readmitted due to cardiovascular and non-cardiovascular causes. In the derivation cohort, 666 (49%) of patients were readmitted at 6 months and 282 (21%) died within 1 year. Six month readmission was associated with an increased 1 year mortality risk in both the derivation cohort [adjusted hazard ratio (aHR) 3.0 (95% confidence interval, CI 2.2-4.0), P < 0.001] and the validation cohort (aHR 1.8, 95% CI 1.4-2.2, P < 0.001). The significant association was similarly observed in AHF (aHR 3.2, 95% CI 2.1-4.9, P < 0.001) and other causes of acute dyspnoea (aHR 2.9, 95% CI 1.9-4.5, P < 0.001), and it did not depend on the aetiology [aHR 2.2, 95% CI 1.6-3.1 for cardiovascular readmissions; aHR 4.1, 95% CI 2.9-5.7 for non-cardiovascular readmissions (P < 0.001 for both)] or timing of readmission. CONCLUSION​S: Our study demonstrated a long-lasting detrimental association between readmission and death in AHF and non-AHF patients with acute dyspnoea. These patients should be considered 'vulnerable patients' that require personalized follow-up for an extended period.