bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variations of SCNA7 and blood pressure potassium interaction
Authors: Delgado C , Delgado-Lelievre M , Lelievre D , Delgado-Almeida A
Published: November 2020

Introduction

The sodium voltage-gated channel alpha subunit 7 (SCN7A) has been associated to renal Na regulation and hypertension. This study explores the relationship between blood pressure (BP) and urinary overnight Na/K ratio (UONaK) in hypertensives (HT) and normotensive (NT) subjects from from National Heart, Lung and Blood Institute funded, Family Blood Pressure Program (FBPP) that were genotyped for 3 SNPs for SCN7A: CV2161217, CV 356958 and CV433036.

Hypothesis

Genetic variations in the SCNA7 are differently associated to BP and UONaK in HT and NT.

Methods

1,749 subjects genotyped for SCN7A SNPs CV2161217, CV 356958 and CV433036 were analyzed from FBPP. Subjects with diastolic BP (DBP) ≥80 or systolic BP (SBP) ≥130 mmHg were classified HTN; subjects with SBP <130 and DBP <80 mmHg were classified as NT. UONAK was calculated by dividing overnight Na by K concentration. Correlation analysis done with partial variables (use of antihypertensive drug, use of diuretics, overnight urine creatinine).

Results

For the CV2161217, HTN group (n=1,030), 52% had C/C, 39% C/T and 9% T/T. In NT group (n=719), 52% had C/C, 38% C/T and 10% T/T. In the HT group, subjects with CC genotype showed strong correlation between DBP and UONaK (Fig 1a) while no significant correlation with SBP. Those with CT genotype maintained the correlation between SBP and UONaK (r=0.10, p=0.03) with no correlation with SBP. The TT showed no correlation between UONaK and SBP or DBP. In the NT, subjects with TT genotype showed strong correlation between DBP and UONaK (Fig 1b) and with SB (r=0.256, p=0.03). Those with CT or TT genotypes showed no correlation between UONaK and SBP or DBP. Similar finding were obtained for CV356958 SNP; no similar association was observed in the CV433036 SNP.

Conclusions

Subjects with the genetic variations in the SCNA7, such as CV2161217 and CV 356958 SNPs, showed significant correlation between blood pressure and overnight urinary sodium potassium. This finding could have important implications in non dipping status observed in some hypertensive patients.

Funding Acknowledgement

Type of funding source: None
The state of platelets and their functional activity in patients with arterial hypertension in combination with non-alcoholic fatty liver disease
Authors: Netiazhenko V , Bazhenova N
Published: November 2020

Background

According to modern concepts of hypertension (HT) and obesity, the hemostatic system in these diseases is characterized by prothrombogenic changes. Since the liver is the site of the formation of many factors of hemostasis, the concomitant non-alcoholic fatty liver disease (NAFLD), which often accompanies the course of both of these diseases, is an actual problem.

Purpose

To improve the efficiency of early diagnosis of thrombophilic blood changes in hypertensive patients with concomitant obesity and NAFLD by determining the state of platelets and their functional activity.

Materials and methods

We examined 167 patients (80 men and 87 women). The average patient age 55.5 [47.0; 61.0] years. Patients were divided into three groups: I - 46 patients with hypertension without NAFLD, II - 54 patients with NAFLD without hypertension, III group - 52 hypertensive patients with NAFLD. The control group consisted of 15 healthy subjects matched for age and sex. Platelet count and mean platelet volume (MPV) was performed on an automated analyzer, spontaneous and induced platelet aggregation was evaluated by laser aggregometer.

Results

A significant increase in the degree of spontaneous aggregation of platelet has been found in patients in all groups compared to the control group: I group - 2.2-fold increasing in aggregation (p<0.05), II group to 4.2-fold (p<0.05), III group had increasing by 4.1-fold (p<0.05).

ADP-induced platelet aggregation was the same in I group and control, but it was 39% higher (p<0.001) in II cohort and by 22.6% (p<0.01) in III group.

Adrenalin-induced platelet activity increased in all groups versus control: I group – 2.1-fold (p<0.001), II group – 2.3-fold (p<0.001), III group – 1.6-fold (p<0.01) elevation.

Arachidonic acid-induced aggregation elevated by 64,2% (p<0.001) in I group and decreased by 56.3% (p<0.01) in II and by 43% (p<0.05) III cohorts.

Collagen-induced activity had not significant difference between groups.

MPV was increased in both groups with NAFLD by 5.9, but in II group significance level was higher - p<0.01 than in group III - p<0.001. MPV had not significant changes in I group versus control.

Conclusion

Spontaneous platelet aggregation is increased in hypertensive patients and it is significantly enhanced in combination with NAFLD. Thus in patients with isolated NAFLD also observed a statistically significant increase in spontaneous aggregation of platelets. That is possibly explained by an increase in MPV which can be considered as one of the NAFLD risk factors thrombophilic changes in primary hemostasis. An analysis of induced platelet aggregation showed that patients with NAFLD may have a lower sensitivity to acetylsalicylic acid therapy.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Bogomolets National Medical University
Telomere length and uric acid in patients with new cases of hypertension according to the 10-year prospective study in urban randomized population
Authors: Podpalova O , Kaliadka M , Babenka A , Mrochek A
Published: November 2020

Objective

To reveal the association between lymphocyte telomere length and serum uric acid level in 10-year prospective randomized study of Belarusian urban population.

Design and method

In 2007/2008 a 10-year prospective study of 3500 persons living in a district of a belarussian city and selected by the random number method started (coverage of the survey was 97.9%). In 2012/2013 according to the results of the second screening 2888 people were examined (coverage of the survey was 84.3%). A 10-year prospective analysis was provided in 2017/2018 and included 145 randomized subjects with hypertension diagnosed in the second screening. Examination of these patients consisted of standard cardiovascular risk factors questionnaires, measurements of blood pressure, blood chemistry, electrocardiography, echocardiography, ultrasound examination of brachiocephalic vessels, real time PCR for the detection of telomere length of peripheral blood lymphocytes.

Results

2171 persons with normal blood pressure and 1257 persons with hypertension were examined in 2007/2008. In the second screening we established 286 new cases of hypertension (14,4% of men and 12,2% of women). According to multifactorial regression analysis, adjusted for age and sex, a significant positive relationship between new cases of hypertension and IV quartile of uric acid level (339–527 μmol/l) was revealed in 5 years (df=1; χ2 Wald=5,1; p<0,05). Regression analysis of 145 randomized subjects of 286 new cases of hypertension showed that, adjusted for age and sex, the IV quartile of uric acid level (339–527 μmol/l), determined in the first screening, was also associated with the I quartile of telomere length in 10 years (df=1; χ2 Wald=4,5; p<0,05). It was investigated that the level of telomere length had a significant negative association with BMI (p<0.05), R wave in aVL (p<0.05), IL-6 level (p<0,05) in these subjects in cross-sectional study in 2017/2018.

Conclusions

Regardless of age and sex, level of serum uric acid ≥339 μmol/l was a risk factor for development of hypertension in randomized population in 5-year prospective analysis and predicted lower telomere length in patients with new cases of hypertension in 10-year prospective analysis.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): State scientific and technical program “Medical and diagnostic technologies”, subprograms “Heart and blood vessels”
Prevalence, pattern and associated cardiovascular risk of t-wave inversion in hypertensive patients: a 5-year follow-up study
Authors: Kasiakogias A , Konstantinidis D , Dimitriadis K , Tatakis F , Zammanis I , Iliakis P , Kouremeti M , Papakonstantinou P , Thomopoulos C , Tsioufis P , Sideris S , Tousoulis D , Tsioufis C
Published: November 2020

Background

Data on prevalence and associated prognosis of repolarization abnormalities among hypertensive patients are limited.

Purpose

We investigated the presence and extent of ST-segment and T-wave changes in a hypertensive population and their predictive ability for cardiovascular disease.

Methods

We studied 1851 white Caucasian hypertensive patients (age 58±12 years, 51%females) without a history of cardiovascular disease for a mean period of 5.3±3.4 years. At the baseline examination, all patients underwent standard 12-lead electrocardiography. T-wave inversion (TWI) was defined as T-wave deflection ≥−0.1 mV in ≥2 contiguous leads,unless associated with bundle branch block. Anterior, lateral or inferior TWI was defined as TWIin leads V2-V4 or V5,V6, I, AVL or II, aVF respectively. Thedepth in millimeters of TWI in each lead was recorded and the maximum depth per location was calculated. ST depression was defined as ≥1mm in depth in two or more contiguous leads.During follow-up, patients underwent clinic visits at least yearly for management of hypertension and risk factors. The outcome studied was theincidence of cardiovascular morbidity set as the composite of non-fatal coronary artery disease and stroke.

Results

In the entire population, prevalence of TWI was 3.8%, of which 39% presented withanterior TWI, 73% withlateral TWI and 11% with inferior TWI. ST depression was observed in 3.6% of patients (anterior in 0.8%, inferior in 0.9% and lateral in 2.6%). Incidence of the composite endpoint during follow-up was 4%. Cox regression analysis revealed that presence of TWI was associated with a significantly greater risk for cardiovascular events (HR: 2.6, 95% CI: 1.1–5.9, p=0.025). The association was stronger for lateral TWI (HR: 3.3, 95%: CI: 1.34–8.30, p=0.01) compared to other locations. In multivariate models controlling for standard confounders these associations were overall sustained. Depth of TWI and presence of ST depression were not associated with cardiovascular risk.

Conclusions

Among hypertensive patients without cardiovascular disease, TWI is infrequent but significantly associated with future cardiovascular events.Lateral TWI carries the worse prognosis

Funding Acknowledgement

Type of funding source: None
Time in blood pressure range for different blood pressure targets and risk of cardiovascular disease: an analysis of a 7-year follow-up registry
Authors: Sideris K , Kasiakogias A , Konstantinidis D , Papakonstantinou P , Tatakis F , Kouremeti M , Tsioufis P , Anastasiou A , Leontsinis I , Manta E , Tousoulis D , Tsioufis C
Published: November 2020

Objective

Recent guideline recommendations have revisited the optimal target blood pressure (BP) for hypertensive patients. The Time in BP Range (TBPR) is an alternative metric for evaluation of long-term achieved BP. We investigated the association of TBPR for different levels of BP control with cardiovascular outcome among treated hypertensives.

Design and method

This is a retrospective analysis of 1202 treated hypertensive patients (age 59±11 years) without a history of cardiovascular disease followed for a mean period of 7±3 years. We calculated the TBPR [(No of Visits in BP range/ Total No of Visits) x 100%] for office systolic BP targets of 130–139mmHg, 120–129mmHg and <120mmHg and examined the associated cardiovascular risk. The outcome studied was the composite of stroke and coronary artery disease. Time spent in systolic BP≥140mmHg served as the reference.

Results

In the entire population, mean TBPR for systolic BP 130–139mmHg, 120–129mmH, and <120mmHg were 26%, 19% and 11% respectively. A TBPR of ≥50% for systolic BP 130–139mmHg, 120–129mmHg and <120mmHg was observed in 332 (28%), 226 (19%) and 107 (9%) patients respectively. The composite endpoint occurred in 54 patients (4.5%). Patients with a TBPR for 120–140mmHg of ≥50% presented with a HR: 0.6 (95% CI: 0.34–1.06) for cardiovascular events. The TBPR of ≥50% for systolic BP 130–139mmHg, 120–129mmHg and <120mmHg was associated with HR of 0.48 (95% CI: 0.23–1.01, p=0.05), 0.64 (95% CI: 0.29–1.39, p=0.26) and 0.72 (95% CI: 0.26–2.05) respectively. This pattern was sustained but further attenuated after controlling for standard risk factors. In comparison, a mean BP across visits of 130–139mmHg, 120–129mmHg and <120mmHg was associated with a HR of 0.54 (5% CI: 0.28–1.03), 0.61 (95% CI: 0.29–1.26) and 0.80 (95% CI: 0.24–2.65).

Conclusions

Among treated hypertensives, a time in BP of 130–140mmHg of more than 50% is associated with the greatest reduction in cardiovascular risk. The TBPR is a potentially useful measure of BP control for evaluation of risk reduction in hypertensive patients.

Funding Acknowledgement

Type of funding source: None
Exhaled air analysis for pulmonary arterial hypertension fingerprints identification
Authors: Swinarew A.S , Kusz B , Skoczynski S , Gabor J , Okla H , Mika B , Skoczylas I , Gasior M , Kopec G , Mizia-Stec K
Published: November 2020

Background

Pulmonary arterial hypertension (PAH) is a rare disease which is often diagnosed in the late phase as its symptoms are non-specific and there is a lack of screening tests. Therefore, there is a strong need for identifying of its biomarkers.

Aim

To identify the biomarkers for PAH in the exhaled breath and in the serum.

Methods

The breath phase of all the patients was collected on the highly porous aseptic material by the use of special patented holder PL 232911. The collected air was then examined with gas chromatography mass spectrometry (GC/MS). For the control of the obtained results plasma of all the patients was examined by the use of Ultra High Performance Liquid Chromatography (UHPLC). A group of 10 patients (2 men, 8 women, mean age 60.4±10.9 years, BMI 27.6±6.0 kg/m2) with diagnosed PAH as well as the group of 10 healthy persons (6 men, 4 women, mean age 35±11 years, BMI 25.6±6.0 kg/m2) were enrolled into the study.

Results

The obtained spectral and chromatographic results clearly presents the qualitative and quantitative QA/QC sensitivity to the metabolites changes in the patient's breath. The identification of changes in ratio of the whole spectra of biomarkers can allow to obtain a multi-dimensional pathways for PAH diagnostics fig. 1. The chromatography data from patients suffering from PAH have been processed by the aid of signal processing toolbox in MATLAB. Only the peaks of the prominence of at least 10000 (experimentally established) have been taken under consideration. The prominence of a peak measures how much the peak stands out due to its intrinsic height and its location relative to other peaks. Next, for the each found peak the arguments of the two neighboring local minima, have been determined and the integration range for calculating the area under the each peak have been established. The ratio of the area under the significant peak to its prominence have been applied for further analysis.

Conclusions

Based on our preliminary results it seems that our method is specific and sensitive in the range of selected bio-fingerprints in patients with PAH. If confirmed on larger population the molecular level breath analysis can be used as a screening test as well as complementary diagnostic method in PAH to the standard clinical practice.

Figure 1. The chromatograms of representative spectra for patients suffering from PAH (red), control (blue) with distinguished significant peaks (presented in the magnification according to their prominence). On the right side, there are the graphical presentation (area/prominence for peaks) of arbitrary chosen patient, but with reference to the original data and for two data approximations obtained by the DWT, which are important in the case of weak separated peaks.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): University of Silesia in Katowice
Dietary approaches to stop hypertension (DASH) diet and blood pressure reduction in adults with and without hypertension: a systematic review and meta-analysis of randomized controlled trials
Authors: Filippou C , Thomopoulos C , Mihas C , Dimitriadis K , Sotiropoulou L , Siafi E , Zammanis I , Dimitriadi M , Chrysochoou C , Nihoyannopoulos P , Tousoulis D , Tsioufis C
Published: November 2020

Background

The dietary approaches to stop hypertension (DASH) diet is recognized as an effective dietary intervention to reduce blood pressure (BP). However, among randomized controlled trials (RCTs) investigating the DASH diet mediated BP reduction,there are significant methodological and clinical differences.

Purpose

The purpose of this study was to comprehensively assess the effect of the DASH diet on BP levels in adults with and without hypertension, accounting for underlying methodological and clinical confounders.

Methods

We systematically searched Medline and the Cochrane Collaboration Library databases and identified 30 RCTs (n=5,545 participants) that investigated the BP effects of the DASH diet compared to a control diet in hypertensive and non-hypertensive adults. Both random-effects and fixed-effect models were used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted.

Results

The DASH diet reduced SBP and DBP significantly more compared to the control diet (difference in means: −3.2 mm Hg; 95% CI: −4.2, −2.3; P<0.001, and −2.5 mm Hg; 95% CI: −3.5, −1.5; P<0.001, respectively). Hypertension status did not modify the effect on BP reduction. The DASH diet compared to the control diet reduced SBP levels to a higher extent in trials with sodium intake >2,400 mg/day compared to trials with sodium intake ≤2,400 mg/day, while both SBP and DBP were reducedmore in trials with mean age <50 years compared to trials of older participants. The quality of evidence was rated as moderate forboth outcomes according to the Grading of Recommendations, Assessment, Development and Evaluation approach.

Conclusion

The adoption of the DASH diet was accompanied by significant BP reduction in adults with and without hypertension, while higher daily sodium intake and younger age enhanced the BP-lowering effect of the intervention. This meta-analysis was registered in the International Prospective Register of Systematic Reviews as CRD42019128120.

Funding Acknowledgement

Type of funding source: None
The mechanisms of age-realted difference of annual changes in ankle-brachial pressure index
Authors: Takahashi T , Tomiyama H , Abyoyans V , Matsumoto C , Nakano H , Iwasaki Y , Fujii M , Shiina K , Chikamori T , Yamashina A
Published: November 2020

In addition to both pulse wave velocity (PWV; a marker of arterial stiffness) and augmentation index (AI; a marker of central hemodynamics), not only the decrease of ankle-brachial pressure index (ABI) but also its increase predict the future cardiovascular events. While arterial stiffness and central hemodynamics have been proposed to affect the increase in ABI logically, their effects on increase in ABI have not been fully clarified. The present cross-sectional and longitudinal studies were conducted to examine the associations of arterial stiffness and central hemodynamics with increase in ABI and also examine the age-related difference of those associations. In 4016 men (42±9 years old), ABI, brachial-ankle PWV (baPWV) and radial AI (rAI) were measured annually for 9 years' observation period. In the cross-sectional analyses adjusted with age, heart rate and mean blood pressure, both baPWV and rAI were associated with ABI in men aged <50, but not in men aged >50. As shown in Figure, ABI was annually increased in subjects aged <50 (n=2870), but not in those aged >50 (n=1146) during the follow-up period. The mixed model linear regression analysis (MMA) conducted in 9 years' annual repeated measurement data demonstrated that increased baPWV (estimate = 0.017, p<0.05) and increased rAI (estimate 0.254, p<0.05) were significant determinant of annual increase of ABI (p<0.01) in men aged <50, but not in men aged >50. In conclusion, the arterial stiffness and central hemodynamics may individually affect the increase in ABI in men aged <50, but not in men >50. Thus, further studies are needed to clarify whether ABI, arterial stiffness, and central hemodynamics individually predicts future cardiovascular events, and their age-related difference of their predictabilities.

figure1

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): Tokyo Medical University
Estimating the burden of hyperkalaemia in the UK in high-risk patient populations
Authors: McEwan P , Hoskin L , Badora K , Sugrue D , James G , Hurst M , Tafesse E
Published: November 2020

Background

Patients with chronic kidney disease (CKD), heart failure (HF), resistant hypertension (RHTN) and diabetes are at an increased risk of hyperkalaemia (HK) which can be potentially life-threatening, as a result of cardiac arrhythmias, cardiac arrest leading to sudden death. In these patients, renin-angiotensin-aldosterone system inhibitors (RAASi), are used to manage several cardiovascular and renal conditions, and are associated with an increased risk of HK. Assessing the burden of HK in real-world clinical practice may concentrate relevant care on those patients most in need, potentially improving patient outcomes and efficiency of the healthcare system.

Purpose

To assess the burden of HK in a real-world population of UK patients with at least one of: RHTN, Type I or II diabetes, CKD stage 3+, dialysis, HF, or in receipt of a prescription for RAASi.

Methods

Primary and secondary care data for this retrospective study were obtained from the UK Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES). Eligible patients were identified using READ codes defining the relevant diagnosis, receipt of indication-specific medication, or, in the case of CKD, an estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73m2 within the study period (01 January 2008 to 30 June 2018) or in the five-year lookback period (2003–2007). The index date was defined as 01 January 2008 or first diagnosis of an eligible condition or RAASi prescription, whichever occurred latest. HK was defined as K+ ≥5.0 mmol/L; thresholds of ≥5.5 mmol/L and ≥6.0 mmol/L were explored as sensitivity analyses. Incidence rates of HK were calculated with 95% confidence intervals (CI).

Results

The total eligible population across all cohorts was 931,460 patients. RHTN was the most prevalent comorbidity (n=317,135; 34.0%) and dialysis the least prevalent (n=4,415; 0.5%). The majority of the eligible population were prescribed RAASi during follow-up (n=754,523; 81.0%). At a K+ threshold of ≥5.0 mmol/L, the dialysis cohort had the highest rate of HK (501.0 events per 1,000 patient-years), followed by HF (490.9), CKD (410.9), diabetes (355.0), RHTN (261.4) and the RAASi cohort (211.2) (Figure 1). This pattern was still observed at alternative threshold definitions of HK.

Conclusion

This large real-world study of UK patients demonstrates the burden of hyperkalaemia in high-risk patient populations from the UK. There is a need for effective prevention and treatment of HK, particularly in patients with CKD, dialysis or HF where increased incidence rates are observed which in turn will improve patient outcomes and healthcare resource usage.

Figure 1. Rates of HK by condition

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): AstraZeneca
Factor analysis for the clustering of cardiometabolic risk factors and sedentary behavior: a VGH-HEALTHCARE substudy
Authors: Tsai T.Y , Lim S.S , Chan S.C , Yang Y.L , Hsu P.F , Wu C.H , Huang S.S , Lin S.J , Pan J.P , Lu T.M , Huang P.H , Leu H.B
Published: November 2020

Background

Few studies have reported the clustering pattern of new CVD risk factors including sedentary behavior, systemic inflammation and cadiometabolic components in the general population.

Purpose

We aimed to explore the clustering pattern of CVD risk factors using exploratory factor analysis to investigate the underlying relationships between various CVD risk factors

Methods

A total of 5606 subjects (3157 male, 51.5±11.7y/o) were enrolled and 14 cardiovascular risk factors including sedentary behaviors and physical inactivity were analyzed in exploratory group (n=3926). The established model was validated with the validation group (n=1676).

Results

Five factor clusters had been identified to explained 69.4% of total variance, including adiposity (BMI, TG, HDL, UA, and HsCRP 21.3%), lipid, (Total cholesterol, and LDL-cholesterol 14.0%), blood pressure (SBP & DBP 13.3%), glucose (HbA1C, fasting glucose 12.9%) and sedentary behavior (MET per week and sitting time per day 8.0%), respectively. HsCRP was clustered with adiposity factors, not other cardiometabolic risk factors. This clustering pattern was verified in the validation group.

Conclusion

Our current study confirmed the clustering structure of cardiometabolic risk factors including sedentary behavior in general population. hsCRP was clustered with adiposity factors while physical inactivity and sedentary behavior were clustered with each other.

Funding Acknowledgement

Type of funding source: None
Sarcopenia-derived exosomal micro-RNA 16-5p exerts the cardio-repair disturbance via pro-apoptotic mechanism in myocardial infarction of mice
Authors: Hayasaka T , Takehara N , Horiuchi K , Kano K , Tomita Y , Yoshida Y , Maruyama K , Minoshima A , Kawabe J , Hasebe N
Published: November 2020

Background

Sarcopenia is a pathophysiological malfunction induced by skeletal muscle atrophy, and several studies reported an association between sarcopenia-induced cardiac cachexia and poor prognosis in heart disease. Since only a few established animal models are recently available, the underlying mechanism of disturbed cardiac repair accompanied with sarcopenia remains poorly understood.

Purpose

We hypothesized that specific microRNAs in sarcopenia-derived exosomes play crucial roles in disturbed cardiac repair with sarcopenia, and these microRNAs directly exacerbate cardiomyocyte injury following cardiac ischemia and reperfusion.

Methods

We developed a novel sarcopenia-induced cardiac repair disturbance mouse model that is induced by tail suspension (TS) 7 days after a 45-min coronary occlusion of cardiac ischemia and reperfusion (I/R). The reduction of the left ventricular ejection fraction (LVEF) after I/R was compared in mice with TS [I/R-TS(+), n=14] and without [I/R-TS(−), n=12] by echocardiography. To investigate the exosomal mechanism of cardiac repair disturbance, a comprehensive analysis of extracted exosomal microRNAs from mice serum was performed in the 2 groups at day 8. Then, we investigated the impact of the identified candidate microRNA in neonatal rat cardiomyocytes (NRVMs). After 4 days in primary culture, candidate microRNA was transfected into NRVMs under hypoxic culture conditions. TUNEL analysis and quantitative PCR analysis of apoptosis-related genes were performed on the NRVMs.

Results

At day 8 after I/R, the LVEF of I/R-TS(+) was not significantly ameliorated compared to that of I/R-TS(−) (ΔLVEF; 1.59±6.92 vs. 8.04±7.71% p=0.034). Four candidate microRNAs obtained from I/R mice serum were identified in the microRNA array analysis. The re-analysis of these candidate micro-RNAs using all I/R mice demonstrated that the level of mir-16-5p in I/R-TS(+) was raised by approximately nine-fold than that in I/R-TS(−) (9.67±13.35 vs. 0.99±1.41, p<0.05). Next, an in vitro experimental model using a microRNA mimic revealed that apoptosis in NRVMs was greatly enhanced by the transfection of a mir-16-5p mimic in hypoxic culture conditions (mir-16-5p vs. control = 5.77±2.84 vs. 1.72±0.55%, p<0.01). Furthermore, by qRT-PCR analysis, the expression of CASP3 and TRP53 were upregulated in NRVMs treated with a mir-16-5p mimic than in control NRVMs.

Conclusion

Myocardial I/R injury in sarcopenia ended in cardiac repair disturbance accompanying with the enhanced expression of exosomal-mir-16-5p. A pro-apoptotic effect of mir-16-5p may exacerbate myocardial I/R injury and thus can be a novel therapeutic target for cardiac repair disturbance in sarcopenia.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Japan Society for the Promotion of Science
Not chronic exercise but acute exercise is related with increased cell survival, enhanced cell proliferation and decreased cell apoptosis
Authors: Postula M , Wicik Z , Eyileten C , Soplinska A , Czajka P , Nowak A , Jarosz-Popek J , Malek L
Published: November 2020

Background

Endurance training can be described as long-time activity characterized by high dynamic and low to high power and was proven beneficial in CVD prevention. Nevertheless, studies reported that excessive endurance training can act as double-edged sword inducing the inflammatory response and cell apoptosis. This negative effect can be the reason of exercise duration.

Purpose

In order to investigate the effect of the training duration we compared and analysed acute vs chronic exercise by using in silico technique and we performed two different bioinformatics analysis: tissue-specific and cardiovascular process specific.

Materials

Bioinformatics analysis miRNA targets predictions, data filtering and visualization as interaction networks were performed. We used multiMiR 1.4 R package, hemopoiesis, angiogenesis, cardiac muscle functions, muscle hypertrophy process was performed a screening of the GO terms for the presence of the key words using the biomaRt package in R, Gene-gene interaction data were retrieved from String App, Cytoscape. Enrichment analysis of Reactome and KEGG pathways using String App. p<0.05.

Results

Enrichment analysis of Reactome and Kegg pathways revealed strong regulation of senescence-related pathways, RUNX1 expression and activity, Ca2+ signaling involving AGO genes. For the first time our in silico analysis showed that AGO, HMGA2 genes may be associated with adaptive changes in response to exercise. Importantly, we found, that PI3K/AKT signalling (pathway incusing cell survival, growth, and proliferation) was present only in acute but not in chronic exercise.

Conclusions

In our analysis long-term training miRNA-gene target interaction was different than the short-term training. As PI3K/AKT signaling was present only in acute exercise, we suggest that not long-term but short-term training can be related with increased cell survival, enhanced cell proliferation, and decreased cell apoptosis.

Genes associated cardiac muscle function

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): “Preludium” from the National Science Center, Poland
Sleep disordered breathing: prevalence and association with cardiovascular disease in the French general population
Authors: Balagny P , Wiernik E , Matta J , Frija-Masson J , Vidal-Petiot E , Steg P.G , Ribet C , Goldberg M , D'Ortho M.P , Zins M
Published: November 2020

Background

Sleep Disordered Breathing (SDB) is highly prevalent and associated with cardiovascular disease (CVD) but many studies have a limited sample size or uncertain generalizability.

Purpose

The aim of this study was to obtain contemporary data on SDB prevalence and to assess its impact on CVD occurrence in a large French population-based sample.

Methods

Data came from participants of the French population-based CONSTANCES cohort, included between 2012 and 2016, with clinical interview, examination and standard biology at inclusion and who were screened for SDB in 2017 using the Berlin Questionnaire (BQ). Follow-up was performed through yearly CONSTANCES questionnaires. CVD occurrence was defined by self-declared myocardial infarction or stroke between 2013 and 2017. Exposure variables were SDB diagnosis on the basis on BQ and its related sleeping symptoms (snoring, apnea and sleepiness). Odds Ratios (OR) were computed with their 95% Confidence Interval (95% CI) and adjusted for age, sex, smoking, dyslipidemia, diabetes, hypertension and body mass index (except for SDB since BQ considers these variables).

Results

Among 54 228 participants, SDB prevalence was 16.1%. Over four years of follow-up, CVD occurred in 2.23% of SDB participants vs 0.72% in non SDB (OR=1.72, 95% CI [1.41–2.09]). CVD occurrence did not increase significantly with snoring (OR=0.95, 95% CI [0.78; 1.17]), but with apnea (OR=1.34, 95% CI [1.05; 1.71]) and with sleepiness (OR=1.42, 95% CI [1.18–1.72] when fatigue occurred after-sleep and OR=1.62, 95% CI [1.33–1.97] during waking time). These associations remained non-significant for snoring regardless of its frequency or noise, were significant for sleepiness as soon as it happened at least once a week and tended to increase with its frequency whenever fatigue occurred (p for trend<0.001). Subgroups analysis in hypertensive and non-hypertensive participants found similar results concerning snoring and sleepiness.

Conclusions

These results confirm that SDB is highly prevalent in the general French population and is associated with a higher occurrence of CVD particularly in sleepy and apneic subjects. Screen for SDB and its symptoms should be relevant to identify high cardiovascular risk people who would benefit from preventive measures.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Plan d'Investissement d'Avenir-3 (PIA3-RHU, Ministry of Health)
The Finnish Diabetes Risk Score (FINDRISC) and incident diabetes and low-grade inflammation
Authors: Pesaro A , Bittencourt M.S , Franken M , Carvalho J.A.M , Silva D.J.B , Santos R.D
Published: November 2020

Background

The Finnish Diabetes Risk Score (FINDRISC) (FR) was developed in Europe to predict type 2 diabetes mellitus (T2DM) risk without need of laboratory tests. Since T2DM is associated with low-grade inflammation, we evaluated the ability of FR to predict either T2DM or elevation in high sensitivity C- reactive protein (CRP), a biomarker of higher cardiovascular risk.

Methods

We included 41,880 subjects (age 41.9±9.7 years; 31% female) who underwent health evaluation between 2008 and 2016 in a single centre in Brazil. The cross-sectional association of FR with T2DM and hs-CRP ≥2.0 mg/L was tested in multivariate models. During a follow-up of 5±3 years, the predictive value of FR for incident T2DM and elevated CRP was tested, respectively, in 10,559 non-diabetic individuals and a subset of 2,816 subjects with baseline low CRP, using logistic regression. Models were adjusted for confounders such as sex, use of medications for dyslipidemia, smoking, and baseline plasma levels of glucose, creatinine and lipids. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative and predictive values of FR for T2DM and CRP ≥2.0 mg/L.

Results

In the cross-sectional analysis, 1,146 (2.7%) individuals had T2DM. In a subgroup of 26,667 individuals in which CRP was measured, 9,229 (34.6%) had CRP ≥2.0 mg / L. During follow-up, there were 364 cases (3.5%) of incidental T2DM, and in the subgroup in which CRP was reassessed (n=2,816 individuals), there were 520 individuals (18.5%) with CRP ≥2.0 mg/L. FR was associated with either T2DM or elevated CRP in cross sectional analysis (respectively, OR 1.24, 95% CI: 1.23–1.26, P<0.001; and OR 1.10, 95% CI: 1.09–1.11, P<0.001; per FR unit), and in longitudinal analysis (respectively OR 1.17, 95% CI: 1.14–1.20, P<0.001; and OR 1.04, 95% CI: 1.02–1.07, P<0.001; per FR unit). In comparison with individuals with low FR, those with moderate, high and very high values showed significant and proportional increases of 3 to 22 fold in the chance of current DMT2 (P<0.001) and 2 to 4 fold in the chance of high CRP (P<0.001). During follow-up, these increases were 2 to 8 fold in the chance of incidental T2DM (P<0.001) and 1.3 to 2 fold in the chance of high CRP (P<0.005). AUC from cross-sectional analysis for DMT2 and CRP ≥2.0 mg/L were respectively 0.82 (95% CI 0.80–0.83) and 0.63 (95% CI 0.63–0.64), and in longitudinal analysis 0.79 (95% CI 0.77–0.82) and 0.54 (95% CI 0.52–0.58), respectively.

Conclusion

FR was associated with the presence and onset of DMT2 and low-grade inflammation, but it predicted better T2DM risk than low-grade inflammation. Therefore, this inexpensive score can be useful for screening and prediction of T2DM. In addition, elevated serum inflammation in individuals with higher FR, may help explain the increased cardiovascular risk in this subset of patients.

Funding Acknowledgement

Type of funding source: None
Association between the FINDRISC score and the risk of metabolic syndrome and hepatic steatosis
Authors: Godoi Bernardes Da Silva D , Dias Santos R , Sommer Bittencourt M , Carvalho J.A.M , Franken M , Pereira Pesaro A.E
Published: November 2020

Introduction

The Finnish Diabetes Risk Score (FINDRISC) was developed in Europe to predict type 2 diabetes mellitus (T2DM) risk without need of laboratory tests. Small cross-sectional studies analyzed the association between RF with metabolic syndrome (MS) or hepatic steatosis (HS). Our objective was to test the association of FINDRISC with MS or HS, in a transversal and longitudinal way.

Methods

In 41,668 individuals (age 41.9±9.7 years; 30.8% women) who underwent health evaluation between 2008 and 2016 in a single centre in Brazil, we tested the transversal association between FINDRISC and MS or HS, in multivariate models. The same analyzes were performed longitudinally in non-diabetic subgroups, followed for 5±3 years, to test the predictive value of FINDRISC and the incidental risk of MS (n=10,075 individuals) or HS (n=7,097 individuals), using logistic regression. Models were adjusted for confounders such as sex, use of medications for dyslipidemia, smoking, and baseline plasma levels of glucose, creatinine and lipids. A receiver operating characteristic (ROC) curve was used to evaluate the discriminative and predictive values of FINDRISC for MS and HS.

Results

In the cross-sectional analysis, 2,252 (5%) individuals had MS and 14,176 (34%) HS. In the longitudinal analysis, there were 302 cases of incidental MS (2%) and 1,096 cases of HS (15%). FINDRISC was independently associated with MS and HS in the cross-sectional analysis (respectively, OR 1.27, 95% CI: 1.25–1.28, P<0.001; and OR 1.21, 95% CI: 1.20–1.22, P<0.001, per FINDRISC unit) and in longitudinal analysis (respectively, OR of 1.18, 95% CI: 1.15–1.21, P<0.001; and OR of 1.10, 95% CI: 1.08–1.11, P<0.001, per FINDRISC unit). In comparison with individuals with low FINDRISC, those with moderate, high and very high values showed significant and proportional increases of the 12 to 77 fold in the chance of current SM (P<0.001) and 3 to 10 fold in the chance of HS (P<0.001). During follow-up, these increases were 3 to 10 fold in the chance of incidental MS (P<0.001) and 1 to 3 fold in the chance of HS (P<0.001). The AUC from cross-sectional analysis for MS and HS were respectively 0.82 (95% CI 0.81–0.83) and 0.76 (95% CI 0.75–0.76), and in longitudinal analysis 0.73 (95% CI 0.70–0.76) and 0.63 (95% CI 0.61–0.65), respectively.

Conclusion

FINDRISC was associated with the presence and onset of MS and HS, but it predicted better metabolic syndrome risk than hepatic steatosis. Therefore, this simple, practical and low-cost score can be useful for population screening and identification of subgroups of individuals at higher risk future metabolic diseases.

Funding Acknowledgement

Type of funding source: None
Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure – a Mendelian randomization study in the FINRISK cohort
Authors: Boerschel C , Geelhoed B , Niiranen T , Havulinna A.S , Fouodo C.J.K , Scheinhardt M.O , Blankenberg S , Jousilahti P , Kuulasmaa K , Zeller T , Salomaa V , Schnabel R.B
Published: November 2020

Background

Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and in previous studies several single nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified.

Purpose

We investigated whether a causal relationship exists between natriuretic peptides and AF as well as HF using a Mendelian randomization approach.

Methods

N-terminal pro B-type natriuretic peptide (NT-proBNP) (N=6669), B-type natriuretic peptide (BNP) (N=6674) and mid-regional pro atrial natriuretic peptide (MR-proANP) (N=6813) were measured in the FINRISK 1997 cohort. Thirty common SNPs related to NT-proBNP, BNP and MR-proANP were selected from prior studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF separately. Polygenic risk scores (PRS) based on multiple SNPs were used as the genetic instrumental variable in Mendelian randomizations.

Results

PRS were significantly associated with the three natriuretic peptides. PRS were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation, other than a weak one, is unlikely.

Conclusion

In our Mendelian randomization approach, based on common genetic variation at the NPPA-NPPB locus, associations of the common polymorphisms with natriuretic peptides and the protein biomarkers themselves with incident disease could be confirmed. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.

Comparison of hazard ratios

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, German Ministry of Research and Education
Resting levels of cardiac markers in athletes
Authors: Kiss O , Frivaldszky L , Tokodi M , Babity M , Bognar C.S , Skopal J , Kovacs A , Vago H , Lakatos B , Zamodics M , Rakoczi R , Czimbalmos C.S , Dohy Z.S , Menyhart-Hetenyi A , Merkely B
Published: November 2020

Introduction

Examination of specific cardiac enzymes and peptide fragments is essential in cases of acute myocardial ischemia and heart failure. According to previous data, exhausting physical effort may cause temporary increase of cardiac necroenzyme levels, while no information is available on their resting values in athletes.

Methods

Resting serum levels of hsTroponinT, CKMB, LDH and NT-proBNP were measured as part of extended sports cardiology screening in healthy athletes and a healthy sedentary non-athlete control group. Depending on normality, groups were compared with two-tailed Student's t-test or Mann-Whitney U-test. Statistical analysis was processed in RStudio integrated development environment.

Results

Results of 237 healthy athletes from different sports (male: 144, age: 19.1±5.9 years, training: 16.0±6.7 hours/week) and 53 sedentary non-athletes (male: 23, age: 19.8±3.2 years, training: 2.6±2.3 hours/week) were analysed. In athletes, increased resting cardiac marker levels were measured as follows: CKMB: 6.3% (n=15), LDH: 3.4% (n=8), hsTroponinT: 4.2% (n=10), NT-proBNP: 0.8% (n=2) of the cases. No elevation of CKMB and hsTroponin T levels were measured in the control group, while only single cases of increased LDH and NT-proBNP were detected. We measured higher levels of CKMB (17.6±7.3 vs. 12.3±3.4 U/l, p<0.001), LDH (322.4±60.8 vs. 286.0±51.1 U/l, p<0.001) and hsTroponinT (6.2±4.7 vs. 4.3±1.4 ng/l, p<0.05), while lower levels of NT-proBNP (23.9±27.2 vs. 49.8±38.7 pg/ml, p<0.001) in athletes compared to the control group. In male athletes, higher levels of CKMB (18.5±6.6 vs. 16.0±8.2 U/l, p<0.001), LDH (337.0±62.2 vs. 300.7±51.9 U/l, p<0.001) and hsTroponinT (7.0±5.3 vs. 4.3±1.9 ng/l, p<0.001), and lower levels of NT-proBNP (19.8±23.1 vs. 35.0±34.1 pg/ml, p<0.001) were measured compared to female athletes. Levels of hsTroponinT decreased in athletes due to increasing age (r=−0.20, p<0.05).

Discussion

According to our results, resting levels of cardiac markers show significant alterations due to sport adaptation of the heart. These changes depend on age and sex as well.

Conclusions

Our research attract attention to different assessment of cardiac markers in athletes in respect of recognition of cardiovascular pathologies.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This project was supported by a grant from the National Research, Development and Innovation Office (NKFIH) of Hungary.
Combined effect of cigarette smoking and prediabetes on structural and functional changes of large arteries
Authors: Ioakeimidis N , Dima I , Terentes-Printzios D , Georgakopoulos C , Angelis A , Gourgouli I , Solomou E , Skoumas I , Tousoulis D , Vlachopoulos C
Published: November 2020

Purpose

Smoking is a major risk factor for cardiovascular disease and prediabetes is associated with excess risks for adverse cardiovascular outcomes and death. Aim of this study was to explore whether smoking and prediabetes exert a synergistic unfavourable effect on functional and structural parameters of large arteries.

Methods

We measured carotid-femoral pulse wave velocity (cfPWV), augmentation index (AIx) and carotid intima media thickness (cIMT) in 407 individuals without known atherosclerotic disease (mean age: 52±8 years) categorized into four age-matched groups according to glucose metabolic and smoking status: Smokers with diabetes (n=68), Smokers with prediabetes (n=87), Non-smokers with prediabetes (n=98) and Non- smokers with normal fasting blood glucose (FBG) (n=154). Prediabetes was defined as impaired fasting glucose (100–125 mg/dL), impaired glucose tolerance (2-hour glucose level of 140–199 mg/dL during an oral glucose tolerance test), or glycosylated hemoglobin (HbA1c) level of 5.7% to 6.4%. High sensitivity C-reactive protein (hsCRP) was measured in all patients.

Results

Systolic pressure, pulse pressure were increased and hsCRP levels were higher in smokers with diabetes compared to the three other groups (overall P<0.05, P<0.01 and P<0.05, respectively, ANOVA). The cumulative tobacco exposure (measured in pack-years) was similar between smokers with diabetes and smokers with prediabetes (45 pack-years). Figure 1 shows cfPWV, AIx and cIMT of the four groups. Interestingly, smokers with diabetes and smokers with prediabetes have similar mean cfPWV and cIMT and significantly higher values compared to non-smokers with prediabetes and non-smokers with normal FBG. The associations remained statistically significant even after adjusting for systolic pressure and hsCRP level. AIx was not different between the four study groups.

Conclusion

The combination of prediabetes and smoking is associated with higher cfPWV and cIMT values compared to prediabetes alone. The smokers with impaired glucose regulation have functional and structural alterations of large arteries similar to that of smokers with established diabetes. Considering the risk for developing prediabetes in relation to smoking status and the number of cigarettes smoked daily and the independent predictive value of assessing vascular changes in large arteries, the present findings may have important clinical and prognostic implications.

Figure 1. Smoking, prediabetes and vascular changes

Funding Acknowledgement

Type of funding source: None