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.

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.

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.

Identifying differential miR and gene consensus patterns in peripheral blood of patients with cardiovascular diseases from literature data.

BACKGROUND: Numerous recent studies suggest the potential of circulating MicroRNAs (miRs) in peripheral blood samples as diagnostic or prognostic markers for coronary artery disease (CAD), acute coronary syndrome (ACS) and heart failure (HF). However, literature often remains inconclusive regarding as to which markers are most indicative for which of the above diseases. This shortcoming is mainly due to the lack of a systematic analyses and absence of information on the functional pathophysiological role of these miRs and their target genes. METHODS: We here provide an-easy-to-use scoring approach to investigate the likelihood of regulation of several miRs and their target genes from literature by identifying consensus patterns of regulation. We therefore have screened over 1000 articles that study mRNA markers in cardiovascular and metabolic diseases, and devised a scoring algorithm to identify consensus means for miRs and genes regulation across several studies. We then aimed to identify differential markers between CAD, ACS and HF. RESULTS: We first identified miRs (miR-122, -126, -223, -138 and -370) as commonly regulated within a group of metabolic disease, while investigating cardiac-related pathologies (CAD, ACS, HF) revealed a decisive role of miR-1, -499, -208b, and -133a. Looking at differential markers between cardiovascular disease revealed miR-1, miR-208a and miR-133a to distinguish ACS and CAD to HF. Relating differentially expressed miRs to their putative gene targets using MirTarBase, we further identified HCN2/4 and LASP1 as potential markers of CAD and ACS, but not in HF. Likewise, BLC-2 was found oppositely regulated between CAD and HF. Interestingly, while studying overlap in target genes between CAD, ACS and HF only revealed little similarities, mapping these genes to gene ontology terms revealed a surprising similarity between CAD and ACS compared to HF. CONCLUSION: We conclude that our analysis using gene and miR scores allows the extraction of meaningful markers and the elucidation of differential pathological functions between cardiac diseases and provides a novel approach for literature screening for miR and gene consensus patterns. The analysis is easy to use and extendable upon further emergent literature as we provide an Excel sheet for this analysis to the community.

Aortic stiffness is an independent determinant of left ventricular diastolic dysfunction in metabolic syndrome patients.

BACKGROUND: We aimed to evaluate the relationship between arterial stiffness and left ventricular diastolic dysfunction (LVDD) in metabolic syndrome (MetS) patients. METHODS: A cross-sectional study was conducted in 1208 subjects without overt atherosclerotic disease. According to the cardiac ultrasound, patients were divided into two groups: with LVDD (LVDD+, n = 1119) and without LVDD (LVDD-, n = 89). Arterial stiffness parameters [carotid-femoral pulse wave velocity (cfPWV) and aortic augmentation index (AIxHR75)] were assessed by applanation tonometry. RESULTS: In comparison to LVDD-, LVDD + patients were older (55 ± 6 vs 51 ± 6 years, p < 0.001), and had higher cfPWV (8.8 ± 1.6 vs 7.9 ± 1.34 m/s, p < 0.001), AIxHR75 (24.7 ± 10.2 vs 19.7 ± 10, p < 0.001), mean arterial pressure (108 ± 12 vs 101 ± 10 mmHg, p < 0.001), heart rate (66 ± 10 vs 61 ± 9 bpm, p < 0.001), left ventricular mass index (LVMI) (109 ± 24 vs 97 ± 22, p < 0.001) and body mass index (BMI) (32 ± 5 vs 30 ± 4 kg/m(2), p < 0.001). We found significant correlations between cfPWV, AIxHR75 and the ratio of early to late transmitral velocities (E/A) (rcfPWV = -0.19, rAIxHR75 = -0.15, p < 0.001), early diastolic mitral annular velocity (E') (rcfPWV = -0.25, rAIxHR75 = -0.18, p < 0.05) and E/E' ratio (rcfPWV = 0.17, rAIxHR75 = 0.14, p < 0.001). Univariate analysis revealed that the presence of LVDD is associated with age [odds ratio (OR) 1.84], BMI (OR 1.63), waist circumference (WC) (OR 1.52), cfPWV (OR 2.18), AIxHR75 (OR 1.55), mean aortic blood pressure (OR 1.94), aortic pulse pressure (OR 1.78), mean common carotid artery intima-media thickness (OR 1.16), heart rate (OR 1.4) and LVMI (OR 1.79) (all p < 0.05). After performing stepwise multiple logistic regression analysis, only cfPWV and BMI or WC remained significant predictors of the presence of LVDD (p < 0.05). CONCLUSION: cfPWV is a significant determinant of LVDD in subjects with MetS.

Association of cardio-ankle vascular index with cardiovascular risk factors and cardiovascular events in metabolic syndrome patients.

OBJECTIVES: We aimed to investigate the association between arterial stiffness assessed as cardio-ankle vascular index (CAVI) and cardiovascular (CV) risk factors and CV events in the middle-aged metabolic syndrome (MS) patients. MATERIALS AND METHODS: A follow-up study was carried out in 2106 middle-aged (53.83±6.17 years old, 62% women) MS subjects without overt atherosclerotic disease. Patients were initially recruited in 2009-2011 as participants of the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program and followed up for 3.8±1.7 years for CV events. Thorough cardiometabolic risk assessment was carried out at inclusion. RESULTS: Subjects with higher CAVI had worse lipid and glucose metabolism profile: elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased high-density lipoprotein cholesterol (HDL-C), higher fasting and oral glucose tolerance test (OGTT) glucose levels (all P<0.001), and lower fasting insulin (P=0.021). Greater age (P<0.001), heart rate (P=0.016), and mean arterial pressure (P<0.001) were also associated with higher CAVI. Over the follow-up period, 93 (4.4%) patients developed a cardiovascular event: 55 (2.6%) patients had myocardial infarction and 38 (1.8%) suffered a cerebrovascular event. Fatal CV events comprised 6.5% (n=6) of all CV events. CAVI was statistically significantly associated with occurrence of myocardial infarction (P=0.027) and total cardiovascular events (P=0.045), but not cerebrovascular events (P=0.65). However, this association was dependent on age and gender. CONCLUSIONS: In the middle-aged MS patients, higher CAVI was associated with altered lipid and glucose metabolism, older age, greater heart rate and mean arterial pressure, and worse cardiovascular outcome.

Prevalence of high-risk profile in middle-aged subjects with arterial hypertension: a nationwide survey.

Hypertension is the most common non-communicable disease and the leading cause of cardiovascular disease in the world. It presents an important public health challenge in both economically developed and developing countries. In 2006, the Lithuanian High Cardiovascular Risk programme was launched. The programme recruited men aged 40-54 and women aged 50-64 without overt cardiovascular disease. We analysed a group of 23,204 subjects included in the programme at the primary level. Arterial hypertension was present in 57.6% of the subjects: 63.2% in the females and 49.2% in the males. In the hypertensive middle-aged subjects, grade 1 hypertension was present in 53.1%, grade 2 in 22.4%, and grade 3 in merely 5.9% of the subjects. The prevalence of a minimum of three concomitant risk factors among the hypertensive patients was 78.0%, compared with 52.1% in the patients without hypertension (p < 0.001). Blood pressure goals were attained in 20.8% of the hypertensive women and in 14.4% of the hypertensive men. In Lithuania, a high prevalence of hypertension was characteristic of middle-aged subjects. Although the blood pressure elevation had not reached high levels, the presence of at least three risk factors concomitant to hypertension was more expressed in them compared with the non-hypertensive subjects.

Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) Comorbidities in Lithuanian National Database: A Cluster Analysis.

Various comorbidities and multimorbidity frequently occur in chronic obstructive pulmonary disease (COPD), leading to the overload of health care systems and increased mortality. We aimed to assess the impact of COPD on the probability and clustering of comorbidities. The cross-sectional analysis of the nationwide Lithuanian database was performed based on the entries of the codes of chronic diseases. COPD was defined on the code J44.8 entry and six-month consumption of bronchodilators. Descriptive statistics and odds ratios (ORs) for associations and agglomerative hierarchical clustering were carried out. 321,297 patients aged 40-79 years were included; 4834 of them had COPD. A significantly higher prevalence of cardiovascular diseases (CVD), lung cancer, kidney diseases, and the association of COPD with six-fold higher odds of lung cancer (OR 6.66; p < 0.0001), a two-fold of heart failure (OR 2.61; p < 0.0001), and CVD (OR 1.83; p < 0.0001) was found. Six clusters in COPD males and five in females were pointed out, in patients without COPD-five and four clusters accordingly. The most prevalent cardiovascular cluster had no significant difference according to sex or COPD presence, but a different linkage of dyslipidemia was found. The study raises the need to elaborate adjusted multimorbidity case management and screening tools enabling better outcomes.

Structure and Distribution of Health Care Costs across Age Groups of Patients with Multimorbidity in Lithuania.

BACKGROUND: Patients with multimorbidity account for ever-increasing healthcare resource usage and are often summarised as big spenders. Comprehensive analysis of health care resource usage in different age groups in patients with at least two non-communicable diseases is still scarce, limiting the quality of health care management decisions, which are often backed by limited, small-scale database analysis. The health care system in Lithuania is based on mandatory social health insurance and is covered by the National Health Insurance Fund. Based on a national Health Insurance database. The study aimed to explore the distribution, change, and interrelationships of health care costs across the age groups of patients with multimorbidity, suggesting different priorities at different age groups. METHOD: The study identified all adults with at least one chronic disease when any health care services were used over a three-year period between 2012 and 2014. Further data analysis excluded patients with single chronic conditions and further analysed patients with multimorbidity, accounting for increasing resource usage. The costs of primary, outpatient health care services; hospitalizations; reimbursed and paid out-of-pocket medications were analysed in eight age groups starting at 18 and up to 85 years and over. RESULTS: The study identified a total of 428,430 adults in Lithuania with at least two different chronic diseases from the 32 chronic disease list. Out of the total expenditure within the group, 51.54% of the expenses were consumed for inpatient treatment, 30.90% for reimbursed medications. Across different age groups of patients with multimorbidity in Lithuania, 60% of the total cost is attributed to the age group of 65-84 years. The share in the total spending was the highest in the 75-84 years age group amounting to 29.53% of the overall expenditure, with an increase in hospitalization and a decrease in outpatient services. A decrease in health care expenses per capita in patients with multimorbidity after 85 years of age was observed. CONCLUSIONS: The highest proportion of health care expenses in patients with multimorbidity relates to hospitalization and reimbursed medications, increasing with age, but varies through different services. The study identifies the need to personalise the care of patients with multimorbidity in the primary-outpatient setting, aiming to reduce hospitalizations with proactive disease management.

Mir-1, miR-122, miR-132, and miR-133 Are Related to Subclinical Aortic Atherosclerosis Associated with Metabolic Syndrome.

Previously, miR-1, miR-122, miR-126, miR-132, miR-133, and miR-370 were found to be related to coronary artery disease (CAD) progression. However, their relationship with subclinical atherosclerosis, especially in subjects with metabolic syndrome, is unknown. Therefore, our aim was to determine their relationship with arterial markers of subclinical atherosclerosis. Metabolic syndrome subjects (n = 182) with high cardiovascular risk but without overt cardiovascular disease (CVD) were recruited from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program. The ardio-ankle vascular index (CAVI), augmentation index normalized to a heart rate of 75 bpm (AIxHR75), aortic pulse wave velocity (AoPWV), and carotid artery stiffness were assessed. MicroRNAs (miRs) were analyzed in serum. Pearson correlation and a univariate linear regression t-test showed that miR-1, miR-133b, and miR-133a were negatively associated with CAVI mean, whereas miR-122 was positively associated. MiR-1, miR-133b and miR-133a, and miR-145 were negatively associated with AIxHR75. MiR-122 correlated negatively with AoPWV. In multivariate linear regression models, miR-133b and miR-122 predicted CAVImean, miR-133 predicted AIxHR75, and miR-122 predicted AoPWV. MiR-132 predicted right carotid artery stiffness, and miR-1 predicted left carotid artery stiffness. The addition of smoking to miR-133b and miR-122 enhanced the prediction of CAVI. Age and triglycerides enhanced the prediction of AoPWV by miR-122. A cluster of four miRs are related to subclinical atherosclerosis in subjects with metabolic syndrome. Combined, they may have a more substantial diagnostic or prognostic value than any single miR. Future follow-up studies are needed to establish their clinical relevance.

Multimorbidity Patterns in the General Population: Results from the EpiChron Cohort Study.

The correct management of patients with multimorbidity remains one of the main challenges for healthcare systems worldwide. In this study, we analyze the existence of multimorbidity patterns in the general population based on gender and age. We conducted a cross-sectional study of individuals of all ages from the EpiChron Cohort, Spain (1,253,292 subjects), and analyzed the presence of systematic associations among chronic disease diagnoses using exploratory factor analysis. We identified and clinically described a total of 14 different multimorbidity patterns (12 in women and 12 in men), with some relevant differences in the functions of age and gender. The number and complexity of the patterns was shown to increase with age in both genders. We identified associations of circulatory diseases with respiratory disorders, chronic musculoskeletal diseases with depression and anxiety, and a very consistent pattern of conditions whose co-occurrence is known as metabolic syndrome (hypertension, diabetes, obesity, and dyslipidaemia), among others. Our results demonstrate the potential of using real-world data to conduct large-scale epidemiological studies to assess the complex interactions among chronic conditions. This could be useful in designing clinical interventions for patients with multimorbidity, as well as recommendations for healthcare professionals on how to handle these types of patients in clinical practice.

Trends in cardiovascular risk factor prevalence among Lithuanian middle-aged adults between 2009 and 2018.

BACKGROUND AND AIMS: The aim of the study was to estimate trends and differences in cardiovascular disease (CVD) risk factor prevalence among middle-aged men and women based on the data from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program between 2009 and 2018. METHODS: A community-based cross-sectional study included men aged 40-54 years and women aged 50-64 years without overt CVD. Nationally representative data comprised 110,370 Lithuanian adults (42.4% men and 57.6% women) examined in the period 2009-2018. Prevalences of major CVD risk factors, such as dyslipidaemia, arterial hypertension, diabetes mellitus, obesity, metabolic syndrome and smoking, were assessed. RESULTS: The study showed a significant drop in the prevalence of dyslipidaemia and TC levels among men (p = 0.030 and p < 0.001) and no significant change among women (p = 0.594 and p = 0.799). The prevalence of AH significantly decreased in both gender groups (p < 0.001 in women and p < 0.001 in men). Obesity rates declined among women while it remained constant among men (p < 0.001 and p = 0.100 respectively). There was a significant decline among women and a significant increase among men in the prevalence of metabolic syndrome (p < 0.001 and p = 0.016 respectively). The prevalence of diabetes increased until 2013, after which it started decreasing in the whole group (p = 0.005). The study showed a significant increase in the percentage of smoking women (p < 0.001), although the number of smoking men remained much higher (about 40%) (p < 0.001). CONCLUSIONS: In our observational study, we have documented a high prevalence of all CVD risk factors in 2009 with a slight decrease during the period in most prevalence rates, except in dyslipidaemia and smoking levels.

Assessing the Pilot Implementation of the Integrated Multimorbidity Care Model in Five European Settings: Results from the Joint Action CHRODIS-PLUS.

Multimorbidity, the coexistence of several chronic conditions in a patient, represents a great challenge for healthcare systems and society. The Integrated Multimorbidity Care Model (IMCM) was recently designed within the Joint Action on chronic diseases and promoting healthy ageing across the life cycle (CHRODIS) to ensure the continuity of care for patients with multimorbidity. The IMCM was implemented in five European pilot sites in Spain, Italy, and Lithuania, within the Joint Action CHRODIS-PLUS. The effect of these pilot interventions was assessed pre- and post-implementation by 17 healthcare managers, using the Assessment of Chronic Illness Care (ACIC) measure, and by 226 patients with the Patient Assessment of Care for Chronic Conditions (PACIC+) survey. The ACIC total score significantly increased (5.23 to 6.71, p = 0.022) after the intervention, with differences across sites. A significant increase in the PACIC+ summary score was found ranging from 3.25 at baseline to 4.03 after the intervention (p < 0.001), and 58% of the sample perceived an improvement in care. Higher PACIC+ scores after the intervention were associated to lower baseline values in the respective PACIC+ dimension and to greater changes in ACIC Part 1 (delivery system organization). The IMCM implementation can help improve the quality of care for patients with multimorbidity.

Arterial Destiffening Starts Early after Renal Artery Denervation.

INTRODUCTION: Renal artery denervation (RDN) is a new widely discussed method in treatment of hypertension. Most of the RDN studies assessed BP and arterial changes 3 and 6 months after the procedure, but there is a lack of trials that investigated early changes after RDN. AIM: To investigate aortic stiffness 24-48 hours after the procedure and thus to examine whether RDN might have an early additive value for a cardiovascular risk decline beyond the lowering of blood pressure. METHODS: RDN was performed for 73 patients with resistant hypertension. Arterial stiffness and central haemodynamics were measured before the procedure, the next day after the procedure, and subsequently after 1, 3, 6, and 12 months. RESULTS: Within 48 hours, RDN significantly reduced aortic pulse wave velocity (AoPWV) from 11.3±2.7 to 10.3±2.6 m/s (p=0.001); reduction was sustained at months 1, 3, 6, and 12. Early changes in the AoPWV value did not correlate with changes in office systolic or diastolic BP (p=0.45; p=0.33). Furthermore, the higher the initial AoPWV value, the greater the reduction of AoPWV observed after 6 months: Q1 8.4±1, Δ0.05±1.6 / Q2 10.1±0.4, Δ1.1±1.4 / Q3 12.2±0.8, Δ1.8±1.7 / Q4 15.3±1.7, Δ2.8±2.1 (p=0.002). CONCLUSIONS: Early and sustained effects on AoPWV observed in our study suggest that RDN may have additional effects on reducing arterial stiffness and cardiovascular risk.

A Methodological Approach for Implementing an Integrated Multimorbidity Care Model: Results from the Pre-Implementation Stage of Joint Action CHRODIS-PLUS.

Patients with multimorbidity (defined as the co-occurrence of multiple chronic diseases) frequently experience fragmented care, which increases the risk of negative outcomes. A recently proposed Integrated Multimorbidity Care Model aims to overcome many issues related to fragmented care. In the context of Joint Action CHRODIS-PLUS, an implementation methodology was developed for the care model, which is being piloted in five sites. We aim to (1) explain the methodology used to implement the care model and (2) describe how the pilot sites have adapted and applied the proposed methodology. The model is being implemented in Spain (Andalusia and Aragon), Lithuania (Vilnius and Kaunas), and Italy (Rome). Local implementation working groups at each site adapted the model to local needs, goals, and resources using the same methodological steps: (1) Scope analysis; (2) situation analysis-"strengths, weaknesses, opportunities, threats" (SWOT) analysis; (3) development and improvement of implementation methodology; and (4) final development of an action plan. This common implementation strategy shows how care models can be adapted according to local and regional specificities. Analysis of the common key outcome indicators at the post-implementation phase will help to demonstrate the clinical effectiveness, as well as highlight any difficulties in adapting a common Integrated Multimorbidity Care Model in different countries and clinical settings.

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.

Multimorbidity care model: Recommendations from the consensus meeting of the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS).

Patients with multimorbidity have complex health needs but, due to the current traditional disease-oriented approach, they face a highly fragmented form of care that leads to inefficient, ineffective, and possibly harmful clinical interventions. There is limited evidence on available integrated and multidimensional care pathways for multimorbid patients. An expert consensus meeting was held to develop a framework for care of multimorbid patients that can be applied across Europe, within a project funded by the European Union; the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS). The experts included a diverse group representing care providers and patients, and included general practitioners, family medicine physicians, neurologists, geriatricians, internists, cardiologists, endocrinologists, diabetologists, epidemiologists, psychologists, and representatives from patient organizations. Sixteen components across five domains were identified (Delivery of Care; Decision Support; Self Management Support; Information Systems and Technology; and Social and Community Resources). The description and aim of each component are described in these guidelines, along with a summary of key characteristics and relevance to multimorbid patients. Due to the lack of evidence-based recommendations specific to multimorbid patients, this care model needs to be assessed and validated in different European settings to examine specifically how multimorbid patients will benefit from this care model, and whether certain components have more importance than others.

Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review.

The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.

Multimorbidity: What do we know? What should we do?

Multimorbidity, which is defined as the co-occurrence of two or more chronic conditions, has moved onto the priority agenda for many health policymakers and healthcare providers. Patients with multimorbidity are high utilizers of healthcare resources and are some of the most costly and difficult-to-treat patients in Europe. Preventing and improving the way multimorbidity is managed is now a key priority for many countries, and work is at last underway to develop more sustainable models of care. Unfortunately, this effort is being hampered by a lack of basic knowledge about the aetiology, epidemiology, and risk factors for multimorbidity, and the efficacy and cost-effectiveness of different interventions. The European Commission recognizes the need for reform in this area and has committed to raising awareness of multimorbidity, encouraging innovation, optimizing the use of existing resources, and coordinating the efforts of different stakeholders across the European Union. Many countries have now incorporated multimorbidity into their own healthcare strategies and are working to strengthen their prevention efforts and develop more integrated models of care. Although there is some evidence that integrated care for people with multimorbidity can create efficiency gains and improve health outcomes, the evidence is limited, and may only be applicable to high-income countries with relatively strong and well-resourced health systems. In low- to middle-income countries, which are facing the double burden of infectious and chronic diseases, integration of care will require capacity building, better quality services, and a stronger evidence base.