333
Small-molecule mediated chemical knock-down of MuRF1 attenuates diaphragm dysfunction in chronic heart failure
V Adams1, TS Bowen2, S Werner3, A Gasch4, D Labeit4, A Linke1, S Labeit4
1TU-Dresden, Heart Center Dresden, Cardiology, Dresden, Germany
2University Leeds, School of Biomedical Science, Leeds, United Kingdom of Great Britain & Northern Ireland
3University Leipzig, Heart Center, Leipzig, Germany
4Institut für Anästhesiologie und Operative Intensivmedizin, Mannheim, Germany
Topic: Basic Science - Cardiac Diseases
Background: Skeletal muscle wasting and weakness develop in several clinical conditions including chronic heart failure (CHF), pulmonary hypertension, cancer, immobilization and sepsis. In CHF, this loss of muscle mass and function occurs in both limb and respiratory muscle and is associated with exercise intolerance, dyspnea, and prognosis. Therefore, reducing muscle wasting as a therapeutic intervention has the potential to modulate quality of life and reduce mortality. In this study, we aimed to assess the efficacy of a recently discovered small-molecule inhibitor of MuRF1 in treating CHF-induced diaphragm myopathy and loss of contractile function.
Methods: Myocardial infarction was induced in mice by ligation of the left anterior descending coronary artery (LAD). Sham operated animals (sham) served as controls. One week post-LAD ligation animals were randomized into 2 groups – one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946 - a recently described MuRF1 interfering small molecule. Echocardiography confirmed development of CHF after 10 weeks. Functional and molecular analysis of the diaphragm (DIA) was subsequently performed.
Results: CHF induced diaphragm fiber atrophy and contractile dysfunction by ~20%, as well as decreased activity of enzymes involved in mitochondrial energy production (P<0.05). Treatment with compound ID#704946 in CHF mice had beneficial effects on the diaphragm: contractile function was protected, while mitochondrial enzyme activity and upregulation of the MuRF1and MuRF2 were attenuated after infarct.
Conclusions: Our murine CHF model presented with diaphragm fiber atrophy, impaired contractile function, and reduced mitochondrial enzyme activities. Chemical knock-down of MuRF1 by ID#704946 appears to be a potential strategy to reverse diaphragm myopathy induced in CHF.
334
Mismatch between self-perceived and calculated cardiometabolic disease risk among participants in a CMD prevention program
DM Stol1, M Hollander1, OC Damman1, MMJ Nielen1, IF Badenbroek1, FG Schellevis1, NJ De Wit1
1Julius Health Center - Julius Gezondheidscentra, Utrecht, Netherlands (The)
On Behalf of: INTEGRATE project
Funding Acknowledgements: ZonMW, LekkerLangLeven, Innovatiefonds Zorgverzekeraars>
Topic: Prevention – Cardiovascular Risk Scores
Objectives: The increasing burden of cardiometabolic diseases (CMD) calls for effective preventive strategies. Inviting people for self-assessment of CMD-risk, through an online risk calculator (ORC), might induce risk reducing behavior. People often have difficulties in understanding the concept of disease risk. Therefore, the objective of this study was to assess the impact of communicating personalized CMD-risk through an ORC on the adequacy of perceived risk and to identify determinants for inadequate risk perception among participants of a prevention program for CMD.
Design: cross-sectional analysis of baseline data from a stepped-wedge randomized controlled trial
Setting: Primary care
Participants: 7,551 participants aged 45-70 years without recorded CMD or CMD risk factors Main outcome measures: 1) difference in participants’(cognitive and affective) risk perception between the intervention group - who completed an ORC and received a personalized CMD-risk estimate- and the control group who answered questions about CMD-risk, but did not receive a personalized CMD-risk estimate; 2) determinants for inadequate risk perception
Results: No differences between the intervention and control group were found in cognitive and affective risk perception (p=0.69 and p=0.17 respectively). ≥85% of the intervention group underestimated their risk and ≤12% overestimated their risk. Family history for DM2 (OR 0.3; 95% CI: 0.2-0.4) and CVD (OR 0.6; 95% CI: 0.4-0.9), BMI ≥27 (OR 0.5; 95% CI: 0.3-0.7) and physical inactivity (OR 0.5; 95% CI: 0.3-0.8) were associated with underestimating CMD-risk.
Conclusions: Communicating personalized CMD-risk did not affect self-perceived risk and a considerable mismatch was found between calculated risk and risk perception. Family history and BMI seem to determine individuals’ risk perception more than risk factors such as age, sex and smoking. We conclude that our participants valued CMD-risk factors differently than objective epidemiological models. A dialogue between patients and clinicians about personal CMD-risk might optimize the effect of the risk information provided.
335
Features of expression and concentration of adiponectin in adipocytes of adipose tissue of different localization in patients with ischemic heart disease
YA Dyleva1, OV Gruzdeva1, EV Belik1, EV Belik1, EG Uchasova1, DA Borodkina1, MY Sinitski1, AV Sotnikov1, KA Kozyrin1, VN Karetnikova1, OL Barbarash1
1Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation
Topic: Basic Science - Cardiac Diseases
Background: Today, obesity is still a serious medical, social and economic problem throughout the world. Among adipokines, adiponectin, which regulates energy homeostasis, influences the metabolism of free fatty acids (FFA) and carbohydrates, which has anti-inflammatory and anti-atherogenic effects, is of particular interest. Adiponectin is synthesized not only by adipocytes, but also by myocytes, including cardiomyocytes.
Purpose: to study the specificity of expression and content of adiponectin in adipocyte culture of subcutaneous, epicardial and perivascular adipose tissue and the influence of various doses of rosuvastatin on these processes.
Methods: Examined 29 patients with ischemic heart disease. Adipocytes were isolated from the samples of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue, and which were taken during coronary artery bypass surgery, followed by cultivation in the presence of rosuvastatin and evaluation of gene expression and adiponectin concentration. All study was carried out in compliance with the Helsinki Declaration, and its protocol was approved by the Ethical Committee of Research Institute. Statistical analysis was performed using Statistica 9.0. All patients gave written informed consent to participate in the study.
Results: Adipocytes SAT, EAT and PVAT differed in the level of adiponectin secretion and expression of its gene. On the first day of cultivation the expression of the adiponectin gene in the EAT was 2.3 times lower than in the PVAT. On the 2nd day of cultivation the expression of the adiponectin gene was reduced both in the EAT and the PVAT as compared to the SAT. When rosuvastatin was added at a concentration of 1 µmol/l, adiponectin gene expression in PVAT was higher than when rosuvastatin was added at a concentration of 5 µmol/l, in the adipocyte culture of SAT effect was opposite
Conclusion: Adipocytes SAT, EAT and PVAT differ in the level of adiponectin secretion and expression of its gene. Rosuvastatin has a multidirectional effect on various fat depots: it reduces expression levels in SAT and increases in PVAT, and low doses of rosuvastatin cause a more pronounced increase in the expression level of the adiponectin gene in PVAT.
336
Effect of a family based randomized controlled trial of cardiovascular risk reduction in individuals with premature family history of coronary heart disease: One-year results of PROLIFIC study.
J Panniyammakal1, S Harikrishnan1, TR Lekha1, S Ganapathi1, S Sivasankaran1, S Padmanabhan2, N Tandon3, D Prabhakaran4
1Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India
2University of Glasgow, Institute of Cardiovascular and Medical Sciences , Glasgow, United Kingdom of Great Britain & Northern Ireland
3All India Institute of Medical Sciences (AIIMS), Department of Endocrinology, New Delhi, India
4Public Health Foundation of India, New Delhi, India
On Behalf of: PROLIFIC
Funding Acknowledgements: Wellcome Trust-DBT India Alliance
Topic: Risk Factors and Prevention – Epidemiology
Background: Family based approaches that target both the structural and environmental conditions in which individuals live may be useful in cardiovascular health promotion in high-risk families. The objective was to assess the efficacy of an integrated care model for managing cardiovascular risk in individuals with family history of premature coronary heart disease (CHD).
Methods: The PROgramme of Lifestyle Intervention in Families for Cardiovascular risk reduction (PROLIFIC Study) was a family based cluster randomized controlled trial in 1678 individuals from 750 families. Eligible families were those with at least one family member with physician confirmed CHD diagnosed before the age of 55 years. After initial screening and risk factor evaluation, each family was randomly assigned to participate in either the intervention arm (integrated CVD risk management) or usual care arm (no interventions other than initial screening) by using computer generated random numbers. The integrated care model involved 1) screening for cardiovascular risk factors, 2) lifestyle interventions by trained non-physician health care workers 3) providing a framework for linkage to appropriate primary health care facility, and 4) active follow-up of intervention adherence. Data on lifestyle, clinical and biochemical characteristics were collected using standardized tools at one-year follow-up. We used models based on Generalised estimating equations (GEE) with an exchangeable working correlation matrix and robust standard errors to assess the impact of the intervention on individual risk factors.
Results: The baseline characteristics were distributed evenly between the two treatment groups. The study population was predominantly women (66%), in the age range of 18-80 years (mean age=40.8 years, SD=14.2), and reasonably well educated (mean years of schooling=13.4 years). Hypertension and diabetes were prevalent in more than one-third (37%), and one-fifth (20%) of the study population, respectively. Frontline health workers conducted a median six visits (IQR: 4-7) to each family in the intervention arm during the one-year intervention period. After one-year, the intervention was effective in achieving 2.67 (95% CI: 1.18 to 4.17) and 1.83 (0.82 to 2.85) mmHg reduction of average systolic and diastolic blood pressure, respectively. Similarly, the intervention model also resulted in reduction in average weight (4.74 kg; 4.10 to 5.38), fasting blood glucose (2.33 mg/dl; -0.97 to 5.65), HbA1c (0.46%; 0.34 to 0.59), total cholesterol (12.50 mg/dl; 9.09 to 15.90) and LDL-cholesterol (10.26 mg/dl; 7.08 to 13.43) at one-year. Tobacco and alcohol use did not differ between treatment groups.
Conclusion: The PROLIFIC study findings suggest that a family-based and frontline-health worker delivered lifestyle intervention model could have a significant public health impact on prevention of CVD among high-risk individuals with family history of premature coronary heart disease in India.
338
miR-1 and miR-133b are associated with failed myocardial reperfusion and worse left ventricular functional recovery in STEMI patients
J A Coelho Lima Junior1, A Mohammed2, S Cormack2, S Jones1, A Ali1, P Panahi1, A Bagnall2, I Spyridopoulos1
1Newcastle University, Institute of Genetic Medicine , Newcastle upon Tyne, United Kingdom of Great Britain & Northern Ireland
2Freeman Hospital, Department of Cardiology, Newcastle upon Tyne, United Kingdom of Great Britain & Northern Ireland
Topic: Secondary Prevention
Background: Failed myocardial reperfusion (FMR) is strongly associated with 1-year incidence of heart failure and mortality in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). It occurs in up to 50% of patients and can be detected as microvascular obstruction (MVO) on cardiac magnetic resonance (CMR) imaging. Muscle-enriched microRNA (miRNA) levels are deregulated following STEMI. Whether they inform about FMR is poorly understood.
Purpose: To investigate the release kinetics of muscle-enriched miRNAs following PPCI and their association with FMR.
Methods: Screening of 179 miRNAs was performed in plasma samples collected at 30min post-PPCI from STEMI patients with MVO (n = 5) and age-matched controls (n = 4) using SYBR-based RT-qPCR panels. The 2 most highly expressed miRNAs were then measured at 13 time points in the initial 3h post-reperfusion in 20 STEMI patients (‘derivation’ cohort) and healthy controls (n = 6). In a ‘validation’ STEMI cohort (n = 50), these 2 miRNAs were quantified at 30 and 90min post-PPCI. All patients had TIMI 0/1 flow pre-PPCI and achieved TIMI 2/3 post-PPCI. In both cohorts, miRNAs were quantified using specific TaqMan small RNA assays by RT-qPCR. In the validation cohort, CMR was performed at 3 days and 3 months post-PCI to determine MVO, infarct size (IS), and LV ejection fraction (LVEF). Mann-Whitney U test or Kruskall-Wallis test with Dunn’s correction were used to assess differences between groups. Correlation between miRNA levels and IS was determined by Spearman’s test.
Results: The muscle-enriched miR-1 and miR-133b were the most highly expressed amongst the screened miRNAs (p < 0.05). In the derivation cohort, miR-1 and miR-133b levels rapidly increased following reperfusion reaching an initial peak at 30min and a second peak at 90min, returning to baseline levels at 24h post-PCI. MVO was detected in 19 (39.5%) patients in the validation cohort. At 90min post-PPCI, miR-1 and miR-133b levels were approximately 3-fold (p = 0.001) and 4.4-fold (p = 0.008) higher in patients with MVO compared to those without MVO, respectively. Levels of miR-1 and miR-133b at 90min post-PCI positively correlated with IS at 3 months post-PPCI [miR-1: r = 0.546, p < 0.001; miR-133b: r = 0.538, p = 0.002]. When patients were divided according to IS tertiles, miR-1 was significantly raised in the highest IS tertile group, which had no change in LVEF over the initial 3 months post-PPCI, compared to the middle (2.7-fold, p = 0.031) and lowest (3.3-fold, p = 0.013) tertile groups, that had significant LVEF improvement.
Conclusion: miR-1 and miR-133b levels increase within 3h of PPCI. They are associated with FMR, the extent of myocardial injury, and worse LV functional recovery post-PPCI. Future studies are warranted to investigate whether these miRNAs are useful tools for risk stratification of STEMI patients with a view to guide secondary prevention post-PPCI.
339
Comparative analysis of age,gender characteristics and comorbidity in patients with history of stroke,myocardial infarction and their combination (RECVASA-CLINICA registry data)
EY Okshina1, MM Lukiyanov1, OM Drapkina1, EY Andreenko1, IS Yavelov1, VG Klyashtorny1, EV Kudryashov1, EN Belova1, AD Deev1, AN Makoveeva1, SA Boytsov2
1National Research Center for Preventive Medicine, Moscow, Russian Federation
2National Medical Research Center for Cardiology, Moscow, Russian Federation
Topic: Peripheral Vascular and Cerebrovascular Disease – Clinical
Aim: To analyze the age and gender characteristics, concomitant cardiovascular and non-cardiovascular diseases (CVD and non-CVD) in patients with history of stroke (HSTR), myocardial infarction (HMI), and their combination (HSTR+HMI) on a basis of the hospital registry.
Methods: 8954 patients with arterial hypertension (AH), coronary artery disease, chronic heart failure (CHF), atrial fibrillation (AF) and their combinations hospitalized to the National Medical Research Center for Preventive Medicine from 01.04.2013 to 31.03.2017 were enrolled in the registry RECVASA-CLINICA. Data of the hospital information system MEDIALOG were analyzed. 2020 (22.6%) patients had a HMI without HSTR, 857 (9.6%) - HSTR without HMI, and 318 (3.6%) had a combination of them.
Results: The age of patients with HMI without HSTR was 66.8±11.3 years and was less than in group HSTR without HMI (70.8±10.9 years) and in the combined group (71.6±9.9 years), p<0.05. Men (70%) prevailed in group HMI without HSTR and women (59%) - in group HSTR without HMI. Gender characteristics in group HMI+HSTR were similar to those in group of HMI without HSTR (64.5% of men, i.e. 1.6 times more than in group HSTR without HMI, p<0.05). In group HMI without HSTR compared with HSTR without HMI and HMI+HSTR groups was lower incidence of: AH (90.2% vs 97.2%; 96.5%); CHF (57.1% vs 40.7; 70.4%); AF (21.2% vs 41.5%; 41.5%), p<0.0001. The number of CVD was: 3.09±0.8 in HMI+HSTR group, 2.9±1.0 in group HMI without HSTR; 1.96±0.9 in HSTR without HMI group. The incidence of diabetes was higher in group HMI+HSTR (35.2%), than in group HSTR without HMI (22.3%) and HMI without HSTR (24.7%), p<0.0001. In group HMI+HSTR were also more often diagnosed: respiratory diseases (37.4% vs 23.9%; 31.9%, p=0.005; p=0,001); kidney diseases (56.6% vs 29%; 44.7%, p<0.0001 and p=0.0003), digestive diseases (80.2% vs 75.6%; 73.4%, p<0.0001 and p=0.025), anemia (12.9% vs 6.9% and 7.9%, p=0.0002 and p=0.009). The proportion of obese patients did not differ significantly in all groups (33.0%; 30.7%; 28.1%, p>0.05). The average number of concomitant non-CVD was: 1.96±0.5 in HMI without HSTR group; 2.03±0.3 in HSTR without HMI group and 2.55±0.3 in group HMI+HSTR (p<0.05). The total number of CVD and non-CVD was maximal in HIM+HSTR group - 5.6; was less in group HMI without HSTR - 4.65 and HSTR without HMI - 3.99.
Conclusions: Patients with combined history of myocardial infarction and stroke had the most unfavorable profile in RECVASA-CLINICA registry: were older, the most comorbide (average number of diseases was more than 5), i.e. had maximal number of CVD, concomitant non-CVD and were characterized by the highest cardiovascular risk. So, the most multidisciplinary approach for the treatment and prevention in this group is necessary. The group of patients with HSTR without HMI was older than HMI without HSTR group, with the prevalence of women (1.6 times more) and had more concomitant non-CVD.
340
Cardiorespiratory fitness lowers the risk of atrial fibrillation (AF) in patients at high risk of AF
P Kokkinos1, C Faselis1, LS Sidossis2, P Karasik1, H Moore1, P Narayan1, J Myers3
1Veterans Affairs Medical Center (VAMC), Washington, United States of America
2Rutgers University, Kinesiology and Health, New Brunswick, United States of America
3Veterans Affairs Health Care System, Palo Alto, United States of America
Topic: Physical Inactivity and Exercise
Background/Introduction: Hypertension, type 2 diabetes mellitus (DM2) and obesity expressed as body mass index (BMI ≥30.0 kg of body weight/m2) all increase the risk for atrial fibrillation (AF). Studies indicate that increased cardiorespiratory fitness (CRF) resulting from moderate intensity aerobic activities attenuates the risk of developing AF. However, it is not known if increased CRF can attenuate AF risk in high-risk patients, defined as having at least two of the three aforementioned risk factors.
Purpose: To evaluate the association between CRF and AF incidence in patients at high risk of developing AF.
Methods: We identified 6,405 patients (mean age 58.0±10.0) with at least two of the following risk factors: HTN, DM2 or BMI ≥30.0 kg of body weight/m2. All participants completed an exercise treadmill test (ETT) as part of their clinical evaluation at the Washington DC., and Palo Alto Veterans Affairs Medical Centers. None had a diagnosis of AF at baseline. Metabolic equivalents (METs) were estimated based on the peak exercise time and treadmill grade. We established four fitness categories based on age-stratified quartiles of peak METs achieved: Least-Fit (4.6±1.2 METs; n=1,292); Low-Fit (6.6±1.2 METs; n=1,752); Moderately-Fit (8.0±1.3 METs; n=1,250); and Highly-Fit (10.7±2.1 METs; n=1,018). Cox proportional hazard models were applied to assess risk of AF. The models were adjusted for age, BMI, resting blood pressure, smoking, race, sleep apnea, chronic kidney disease, dyslipidemia, and CV/antihypertensive medications. The Least-Fit category served as the referent. P-values <0.05 using two sided tests were considered statistically significant.
Results: During a median follow-up period of 10.6 years, there were 679 incidences of AF (10.6%) or 11.9 events per 1000 person-years of follow-up. The association between exercise capacity and the risk for developing AF was inverse and graded. For every 1-MET increase in exercise capacity the AF-risk was 13% lower (HR=0.87; CI: 0.85-0.90; p<0.001). When compared to the Least-Fit category, the AF risk was 33% lower for the Low-Fit individuals (HR=0.67; CI: 0.55-0.82; p<0.001); 44% lower for the Moderate-Fit (HR=0.56; CI: 0.45-0.69; p<0.001) and 59% lower (HR=0.41; CI: 0.33-0.52; p<0.001) for High-Fit individuals.
Conclusion: Increased cardiorespiratory fitness attenuates the risk for developing AF in individuals at high-risk for developing AF. The association is inverse, independent and graded.
341
Objectively measured prevalence and time trends of obesity and severe obesity in 447 925 Swedish adults, 1995-2017
E Hemmingsson1, O Ekblom1, LV Kallings1, G Andersson2, P Wallin2, J Soderling3, B Ekblom1, V Blom1, E Ekblom-Bak1
1Swedish School of Sports and Health Sciences, Stockholm, Sweden
2HPI Health Profile Institute, Stockholm, Sweden
3Karolinska Institute, Stockholm, Sweden
Funding Acknowledgements: The study was supported by the Swedish Research Council for Health, Working Life and Welfare (FORTE, Dnr 2018-00384) and the Swedish Armed Forces.
Topic: Obesity
Background: The prevalence of obesity in Sweden has generally been low from a European perspective, although estimates (particularly for adults) have largely relied on self-report data in non-representative samples.
Purpose: To describe the current prevalence estimate of obesity (BMI ³30 kg/m2) and severe obesity (BMI ³35 kg/m2), with accompanying time trends in obesity and severe obesity between 1995 and 2017, in a large and nationally-representative sample of Swedish adults.
Methods: Data on height, weight, age, gender, education and geographical region were obtained in n=447 925 Swedish citizens through a nationwide occupational health service screening test (HPI Health Profile Assessment Test). In order to account for variations between sampling periods for important obesity prognostic variables (age, gender, education, region), we quantified prevalence estimates and time trends using standardized values (direct method) to the entire population of 18-74 year olds in Sweden in 2015, using nationwide databases. Overall estimates as well as separate estimates across gender, age, education and regional categories were calculated. Years were grouped into two-year periods (except the first period where we used three years) for reduced sampling variations and increased power. We used multivariable logistic regression to quantify independent associations between age, gender, education and region with obesity development and current prevalence rates.
Results: In 2016/17 the prevalence of obesity and severe obesity were 16.6% and 4.2%, respectively. Factors associated with higher obesity rates were male gender, older age, lower education and rural region (all P<0.001). For severe obesity, we noted clear prevalence differences between low vs high education (6.3 vs 2.2%), and rural vs urban region (5.6% vs 3.2%), both P<0.001. Between 1995 to 2017, rates of obesity and severe obesity increased by 3.8% and 5.2% per annum, respectively (P<0.001 for both). While prevalence rates increased across all prognostic categories, low education (vs high) and rural region (vs urban) experienced higher increases in obesity and severe obesity.
Conclusion: In this large sample using objective data, the prevalence of obesity and severe obesity in Sweden during 2016/17 were 17% and 4%, still reasonably low in a European perspective. Trend analyses, however, revealed a steady increase of obesity and particularly severe obesity across society. Priority groups for prevention efforts include individuals with low education and those living in rural areas.
