Implications of pulse wave velocity and central pulse pressure in heart failure with reduced ejection fraction.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) and central pulse pressure (PP) are recognised as significant indicators of vascular health and predictors of cardiovascular outcomes. In this study, associations between central hemodynamics and left ventricular (LV) echocardiographic parameters were investigated in subjects with heart failure with reduced ejection fraction (HFrEF), comparing the results to healthy individuals. METHODS AND RESULTS: This cross-sectional prospective controlled study included 50 subjects with HFrEF [mean LV ejection fraction (EF) 26 ± 6.5%] and 30 healthy controls (mean LVEF 65.9 ± 5.3%). Pulse wave analysis (PWA) and carotid-femoral pulse wave velocity (cfPWV) were used to measure central hemodynamics and arterial stiffness. The HFrEF group displayed higher cfPWV (8.2 vs. 7.2 m/s, p = 0.007) and lower central (111.3 vs. 121.7 mmHg, p = 0.001) and peripheral (120.1 vs. 131.5 mmHg, p = 0.002) systolic blood pressure. Central pulse pressure (PP) was comparable between the two groups (37.6 vs. 40.4 mmHg, p = 0.169). In the HFrEF group, cfPWV significantly correlated with left ventricular end-diastolic volume (LVEDV) index (mL/m2) and LVEF, with LVEDV index being a significant independent predictor of cfPWV (R2 = 0.42, p = 0.003). Central PP was significantly associated with heart rate, LVEF and LVEDV index, with the latter being a significant independent predictor of central PP (R2 = 0.41, p < 0.001). These correlations were not observed in healthy controls. CONCLUSIONS: Significant associations between central hemodynamic measures and LV echocardiographic parameters were identified, suggesting the potential to use PWA and cfPWV as possible tools for managing HFrEF.

What is the context?Heart failure with reduced ejection fraction (HFrEF) affects millions of people worldwide.Vascular health plays a significant role in the development and progression of HFrEF.This study investigates two indicators of arterial stiffness­pulse wave velocity (PWV) and central pulse pressure (PP)­and their impact on the functioning of the heart in HFrEF patients compared to healthy individuals.What is new?The study found that higher carotid-femoral PWV and central PP, which typically indicate worse vascular health, were associated with better heart function in HFrEF patients. This paradoxical finding suggests that in the context of HFrEF, traditional markers of vascular health may have different implications.The study included non-invasive methods to evaluate these indicators, offering a potential new additional approach for monitoring and managing HFrEF.What is the impact?We could possibly use non-invasively evaluated PWV and central PP (measures of vascular function) as markers of left ventricular function assessment in HFrEF.

Lifeday coverage of oral anticoagulants and one-year relative survival in patients with atrial fibrillation: a population-based study in Estonia.

BACKGROUND: Routine oral anticoagulation (OAC) is recommended for almost all high-risk patients with atrial fibrillation, yet registries show that OACs are still underused. Our aim was to study the lifeday coverage (LDC) of OAC prescriptions and its relationship with one-year mortality rates of AF patients aged ≥ 65 in Estonia for the years 2019 and 2020. METHODS: Medical data for AF patients aged ≥ 65 years from 2018 and alive as of 01.01.2019 (cohort I) and new AF documentation from 2019 and alive as of 01.01.2020 (cohort II) was obtained from the Health Insurance Fund's electronic database. The data was linked to the nationwide Estonian Medical Prescription Centre's database of prescribed OACs. For LDC analysis, daily doses of guideline-recommended OACs were used. The patients were categorized into three LDC groups: 0%, 1-79%, and ≥ 80%. The data was linked to the Estonian Causes of Death Registry to establish the date of death and mortality rate for the whole Estonian population aged ≥ 65. RESULTS: There were 34,018 patients in cohort I and 9,175 patients with new AF documentation (cohort II), previously not included in cohort I. Of the patients, 77.7% and 68.6% had at least one prescription of OAC in cohorts I and II respectively. 57.4% in cohort I and 44.5% in cohort II had an LDC of ≥ 80%. The relative survival estimates at 1 year for LDC lifeday coverage groups 0%, 1-79%, and ≥ 80% were 91.2%, 98.2%, and 98.5% (cohort I), and 91.9%, 95.2%, and 97.6% (cohort II), respectively. CONCLUSIONS: Despite clear indications for OAC use, LDC is still insufficient and anticoagulation is underused for stroke prevention in Estonia. Further education of the medical community and patients is needed to achieve higher lifeday coverage of prescribed OACs.

Adherence to recommendations for secondary prevention medications after myocardial infarction in Estonia: comparison of real-world data from 2004 to 2005 and 2017 to 2018.

BACKGROUND: Relatively high rates of adherence to myocardial infarction (MI) secondary prevention medications have been reported, but register-based, objective real-world data is scarce. We aimed to analyse adherence to guideline-recommended medications for secondary prevention of MI in 2017 to 2018 (period II) and compare the results with data from 2004 to 2005 (period I) in Estonia. METHODS: Study populations were formed based on data from the Estonian Health Insurance Fund's database and on Estonian Myocardial Infarction Register. By linking to the Estonian Medical Prescription Centre database adherence to guideline-recommended medications for MI secondary prevention was assessed for 1 year follow-up period from the first hospitalization due to MI. Data was analysed using the defined daily dosages methodology. RESULTS: Total of 6694 and 6060 cases of MI were reported in periods I and II, respectively. At least one prescription during the follow up period was found for beta-blockers in 81.0% and 83.5% (p = 0.001), for angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) in 76.9% and 66.0% (p < 0.001), and for statins in 44.0% and 67.0% (p < 0.001) of patients in period I and II, respectively. P2Y12 inhibitors were used by 76.4% of patients in period II. The logistic regression analysis adjusted to gender and age revealed that some drugs and drug combinations were not allocated similarly in different age and gender groups. CONCLUSIONS: In Estonia, adherence to MI secondary prevention guideline-recommended medications has improved. But as adherence is still not ideal more attention should be drawn to MI secondary prevention through systematic guideline implementation.

Effect of Half-Marathon Running on Arterial Stiffness and Blood Biomarkers in High-Level and Recreational Male Athletes.

There is no clear understanding about the effect of intensive physical load on arterial stiffness and related biomarkers. The aim of this study was to evaluate the effect of half-marathon running on arterial stiffness and blood biomarkers during post-competitive recovery period in competitive and recreational male athletes. Eleven high-level long-distance runners (27.1 ± 4.8 yrs) and seven recreational athletes (34.3 ± 6.1 yrs), who participated in a half-marathon run were examined. Blood biomarkers and arterial stiffness (SphygmoCor 7.1) were measured at baseline and at 18 to 22 hours after the competition. There were no statistically significant changes between the groups in augmentation index (AIx, AIx@75) or pulse wave velocities at carotid-femoral segment (cfPWV) during recovery period. Between-group comparison did not reveal significant differences in blood pressure and arterial stiffness values at baseline and during recovery period. The change of cfPWV (difference between cfPWV at baseline and cfPWV during post-competitive recovery period) was significantly dependent on race time and sports level of the athlete (high-level or recreational). A significant increase was found in hsCRP, creatine kinase and LDH activity during the post-race period in both groups. No significant changes were found in oxidative stress markers in the groups after the race except for higher diene conjugates level in recreational athletes in comparison with the high-level group during recovery period. Our study results showed that half-marathon competition did not cause any significant changes in arterial stiffness parameters during the recovery period. However, the change in cfPWV was independently associated with half-marathon race time and the athlete's level of training revealing a mild increase of arterial stiffness in high-level athletes and athletes with a faster race time.

Remote Ischaemic Preconditioning Attenuates Cardiac Biomarkers During Vascular Surgery: A Randomised Clinical Trial.

OBJECTIVE: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on preventing the leakage of cardiac damage biomarkers in patients undergoing vascular surgery. METHODS: This is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 minutes of ischaemia, followed by 5 minutes of reperfusion, was applied. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia. High sensitivity troponin T level was measured preoperatively and 2, 8 and 24 hours after surgery and pro b-type natriuretic peptide was measured preoperatively and 24 hours after surgery. RESULTS: There was significantly higher leakage of high sensitivity troponin T (peak change median 2 ng/L, IQR 0.9-6.2 ng/L vs 0.6 ng/L, IQR 0.7-2.1 ng/L, p = .0002) and pro b-type natriuretic peptide (change median 144 pg/mL, IQR 17-318 pg/mL vs 51 pg/mL, IQR 12-196 pg/mL, p = .02) in the sham group compared to the RIPC group. CONCLUSION: RIPC reduces the leakage of high sensitivity troponin T and pro b-type natriuretic peptide. Therefore, it may offer cardioprotection in patients undergoing non-cardiac vascular surgery. The clinical significance of RIPC has to be evaluated in larger studies excluding the factors known to influence its effect.

Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia.

PURPOSE: Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, and describe health outcomes affected by such a strategy. METHODS: The Estonian Biobank of Estonian Genome Center, University of Tartu, comprises 52,274 individuals. Among 4776 participants with exome or genome sequences, we identified 27 individuals who carried FH-associated variants in the LDLR, APOB, or PCSK9 genes. Cascade screening of 64 family members identified an additional 20 carriers of FH-associated variants. RESULTS: Via genetic counseling and clinical management of carriers, we were able to reclassify 51% of the study participants from having previously established nonspecific hypercholesterolemia to having FH and identify 32% who were completely unaware of harboring a high-risk disease-associated genetic variant. Imaging-based risk stratification targeted 86% of the variant carriers for statin treatment recommendations. CONCLUSION: Genotype-guided recall of probands and subsequent cascade screening for familial hypercholesterolemia is feasible within a population-based biobank and may facilitate more appropriate clinical management.

Effects of Remote Ischaemic Preconditioning on Arterial Stiffness in Patients Undergoing Lower Limb Angiographic Procedures: A Randomised Clinical Trial.

OBJECTIVES: Remote ischaemic preconditioning (RIPC) is a phenomenon that promotes protection of tissues and organs against ischaemia reperfusion injury. RIPC has been shown to reduce myocardial and renal injury but its effect on arterial stiffness in patients undergoing lower limb digital subtraction angiography (DSA) is unknown. The aim of this study was to evaluate the effect of RIPC on arterial stiffness in patients with peripheral arterial disease (PAD) undergoing lower limb DSA. METHODS: In the RIPC intervention, the blood pressure cuff on the arm was inflated to 200 mmHg or to 20 mmHg above systolic pressure, and in the sham intervention to 20 mmHg. For both, the procedure was repeated for four five minute cycles at five minute intervals between the cycles. Changes in heart rate corrected augmentation index (AIx@75), augmentation index (AIx), carotid femoral pulse wave velocity (PWV), and haemodynamic parameters were measured before and 24 h after DSA. RESULTS: 111 (RIPC 54, sham 57) patients with symptomatic lower limb PAD scheduled for DSA were randomised. 102 patients (RIPC 47, sham 55) were included in final analysis. RIPC significantly improved AIx (-5.46% in RIPC and -1.45% in sham group; p = .05), but not AIx@75 (-4.88% in RIPC and -1.38% in sham group; p = .07) or PWV (-0.41 m/s in RIPC and -0.27 m/s in sham group; p = .74). In the RIPC group a significant reduction in AIx (p = .002) and AIx@75 (p = .003) was noted after stenting when compared with the sham intervention. AIx (p = .001), AIx@75 (p = .002), mean arterial (p = .01), peripheral (p = .02), and central systolic blood pressure (p = .006) were significantly reduced only in the RIPC group 24 h after DSA. CONCLUSION: This study evaluates for the first time the effects of RIPC on arterial stiffness parameters in patients with symptomatic PAD following DSA. RIPC may modulate arterial stiffness following a DSA procedure and is more pronounced in patients after stent placement.

The Effect of Remote Ischaemic Preconditioning on Arterial Stiffness in Patients Undergoing Vascular Surgery: A Randomised Clinical Trial.

OBJECTIVES: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on arterial stiffness in patients undergoing vascular surgery. METHODS: This was a randomised, sham controlled, double blind, single centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited. A RIPC or a sham procedure was performed, using a blood pressure cuff, along with preparation for anaesthesia. The RIPC protocol consisting of four cycles of 5 min of ischaemia, followed by 5 min of reperfusion was applied. Arterial stiffness and haemodynamic parameters were measured pre-operatively and 20-28 h after surgery. Two primary outcomes were selected: augmentation index and pulse wave velocity. RESULTS: Ninety-eight patients were randomised. After dropouts 44 and 46 patients were included in the RIPC and sham groups, respectively. Both groups were comparable. There were no statistically significant differences in augmentation index (p = .8), augmentation index corrected for heart rate of 75 beats per minute (p = .8), pulse wave velocity (p = .7), large artery elasticity indices (p = .8), small artery elasticity indices (p = .6), or mean arterial pressure (p = .7) changes between the RIPC and sham groups. There occurred statistically significant (p ≤ .01) improvement in augmentation index (-5.8% vs. -5.5%), augmentation index corrected for a heart rate of 75 beats per minute (-2.5% vs. -2%), small artery elasticity indices (0.7 mL/mmHg × 100 vs. 0.9 mL/mmHg × 100), and mean arterial pressure post-operatively in both the RIPC and the sham groups (change median values in RIPC and sham groups, respectively). CONCLUSIONS: RIPC had no significant effect on arterial stiffness, but there was significant improvement in arterial stiffness after surgery in both groups. Arterial stiffness and haemodynamics may be influenced by surgery or anaesthesia or oxidative stress or all factors combined. Further studies are needed to clarify these findings. CLINICALTRIALS.GOV: NCT02689414.

Oxidative Stress Parameters and Its Associations With Arterial Stiffness in Competitive Powerlifting Athletes After 12-Week Supervised Strength Training.

Jürgenson, J, Serg, M, Kampus, P, Kals, J, Zagura, M, Viru, M, Zilmer, K, Zilmer, M, Eha, J, and Unt, E. Oxidative stress parameters and its associations with arterial stiffness in competitive powerlifting athletes after 12-week supervised strength training. J Strength Cond Res 33(7): 1816-1822, 2019-Available studies have not revealed a clear understanding of the impact of intensive strength training on arterial stiffness and oxidative stress (OxS) parameters, which may have a significant impact on further cardiovascular health of an athlete. The purpose of this study was to evaluate the effect of a 12-week supervised strength training program (SSTP) on oxidative stress indices and its relationship with arterial stiffness in powerlifting athletes. A total of 19 men (28 ± 6 years) exercised for 12 weeks (4 days per week with intensity 60-90% assessed from 1 repetition maximum, 90-120 minutes per session). Oxidative stress parameters and arterial stiffness (SphygmoCor 7.1) were measured before and after SSTP. The study results showed that total peroxide concentration increased and total antioxidant capacity decreased significantly after SSTP. There were no significant changes in carotid-femoral pulse wave velocity (cfPWV) or in the augmentation index. Correlation analysis revealed that the magnitude of the increase of cfPWV was significantly related to the increase of OxS. The current study demonstrated that a 12-week SSTP in powerlifting athletes produced significant changes in OxS indices, which were positively related to increased aortic stiffness. This novel finding may have significant implications about the effect of OxS on cardiovascular health after high-intensity strength training. Furthermore, strength and conditioningcoaches may have to consider the long-term exercise-induced changes in OxS on an individual level, where increased OxS leads to impaired arterial stiffness and cardiovascular health.

Early Biomarkers of Renal Damage in Relation to Arterial Stiffness and Inflammation in Male Coronary Artery Disease Patients.

BACKGROUND/AIMS: Plasma neutrophil gelatinase-associated lipocalin (NGAL), urinary liver-type fatty acid-binding protein (L-FABP) and urinary kidney injury molecule-1 (KIM-1) have emerged as promising biomarkers for both acute and chronic kidney injury that also provide prognostic value for cardiovascular morbidity and mortality. Our aim was to evaluate their relationships with arterial stiffness and inflammation in coronary artery disease (CAD) patients and in clinically healthy controls. METHODS: We studied 52 patients with CAD (age 63.2 ± 9.2 years) and 41 healthy controls (age 60.1 ± 7.2 years). Urinary L-FABP and KIM-1 as well as serum NGAL, adiponectin and resistin levels were measured using the enzyme-linked immunosorbent assay method. The technique of applanation tonometry was used for non-invasive pulse wave analysis and pulse wave velocity assessments. RESULTS: Urinary L-FABP and KIM-1 were independent determinants of cf-PWV for the CAD patients (R2=0.584, P<0.001) but not for the controls. Adiponectin correlated with log-KIM-1 (r=0.31, P=0.028) only for the patients, while NGAL correlated with WBC count (rho=0.29, P=0.038; r=0.35, P=0.029) and resistin (rho=0.60, P<0.001; r=0.57, P<0.001) for both the CAD and control groups, respectively. CONCLUSION: Our findings suggest that urinary L-FABP and KIM-1 may be independently associated with aortic stiffness in individuals with CAD.

The acute effects of passive heat exposure on arterial stiffness, oxidative stress, and inflammation.

BACKGROUND AND OBJECTIVE: The aim of the study was to determine the acute effect of passive heat exposure (PHE) on arterial stiffness, oxidative stress (OxS) and inflammatory parameters. MATERIALS AND METHODS: Subjects were studied in thermoneutral conditions before and after PHE in a climatic chamber. Pulse wave analysis was used for assessment of central hemodynamic and arterial stiffness parameters. Venous blood samples were obtained to measure OxS and inflammatory parameters. RESULTS: Rectal temperature increased after PHE exposure compared to baseline: 37.01°C±0.19°C and 36.4°C±0.31°C, respectively (P<0.001). There was a 17% (P<0.05) decrease in large artery elasticity index (from 24.68±5.53 to 20.42±2.65mL/mmHg*10), which was predicted upon normothermic value (r=-0.878, P<0.01). However, no significant changes were found in others arterial stiffness parameters. A 30% (P<0.05) increase occurred in blood IL-6 concentration (from 0.43±0.15 to 0.56±0.23pg/mL), but OxS parameters remained significantly unchanged. CONCLUSIONS: This study describes for the first time acute PHE effects on arterial stiffness, inflammation and OxS. PHE significantly decreases large artery elasticity index and increases inflammatory IL-6 level. However, further larger investigations are needed for clarifying acute PHE effects on arterial function and biomarkers.

The Association Analysis between ACE and ACTN3 Genes Polymorphisms and Endurance Capacity in Young Cross-Country Skiers: Longitudinal Study.

Endurance performance depends on the integration of several phenotypic traits influenced by multiple environmental and genetic factors. Objectives of the study were: (1) to examine the genotypic frequencies of the ACE I/D, ACTN3 R577X polymorphisms and endurance performance-related phenotypes, (2) to evaluate the dynamics of endurance performance parameters during a 5-year period in relation to ACE I/D and ACTN3 R577X genotypes in Estonian young skiers. Determination of VO2peak was performed in 58 skiers aged 15-19 years (41 males, 17 females) during a 5-year period. The control group consisted of 322 healthy non-athletic subjects (145 males, 177 females). The study groups were genotyped for the ACE I/D and ACTN3 R577X variants. Frequencies of the ACE ID and ACTN3 RR genotypes were significantly higher (p = 0.047 and p = 0.003, respectively) and the RX genotype was lower (p = 0.008) in young male skiers compared with controls. A significant relationship was found between change (Δ) of training volume and ΔVO2peak (mL·kg(-1)·min(-1)) (r = 0.475, p = 0.002). No significant main effect was detected between VO2peak (mL·kg(-1)·min(-1)) dynamics (comparison with the previous age group data) and ACE I/D and ACTN3 R577X genotypes interactions (F = 0.571, p = 0.770 and F = 0.650 and p = 0.705, respectively) in all young skiers. Study results indicated a significantly higher frequency of the ACE ID and ACTN3 RR genotypes among Estonian young male skiers compared with the male control group. Significant genotype-related differences in dynamics of VO2peak during a 5-year period were not found. In the future, longitudinal research including different gene variants may contribute to a better understanding of the nature of endurance performance. Key pointsSignificantly higher prevalence of the ACE ID and the ACTN3 RR genotypes were found among Estonian young male skiers compared with the male control group, which may be an advantage for the explosive speed and power capacity in race skiing.A more remarkable trend of increase in VO2peak (mL·kg(-1)·min(-1)) during the 5-year period was observed among male skiers with the ACTN3 XX genotype and among female skiers with the ACE ID genotype.No significant genotype-related associations in the dynamics of VO2peak were found during the 5-year period.

Improved treatment and prognosis after acute myocardial infarction in Estonia: cross-sectional study from a high risk country.

BACKGROUND: The aim of the study was to explore trends in short- and long-term mortality after hospitalization for acute myocardial infarction (AMI) over the period 2001─2011 in Estonian secondary and tertiary care hospitals while adjusting for changes in baseline characteristics. METHODS: In this nationwide cross-sectional study random samples of patients hospitalized due to AMI in years 2001, 2007 and 2011 were identified and followed for 1 year. Trends in 30-day and 1-year all-cause mortality were analysed using Cox proportional hazards regression model. RESULTS: The final analysis included 423, 687 and 665 patients in years 2001, 2007 and 2011 respectively. During the study period, the prevalence of most comorbidities remained unchanged while the in-hospital and outpatient treatment improved significantly. For example, the proportion of tertiary care hospital AMI patients who underwent revascularization was almost three times higher in 2011 compared to 2001. The proportion of secondary care patients who were referred to a tertiary care centre for more advanced care increased from 5.8 to 40.1 % (p for trend <0.001). Meanwhile, the 1-year mortality rates decreased from 29.5 to 20.2 % (adjusted p = 0.004) in the tertiary and from 32.4 to 23.1 % (adjusted p = 0.006) in the secondary care. The decrease in the 30-day mortality rates was statistically significant only in the secondary care hospitals. CONCLUSIONS: The use of evidence-based treatments in Estonian AMI patients improved between 2001 and 2011. At the same time, we observed a significant reduction in the long-term mortality rates, both for patients primarily hospitalized into secondary as well as into tertiary care hospitals.

Effects of RIPC on the Metabolomical Profile during Lower Limb Digital Subtraction Angiography: A Randomized Controlled Trial.

Remote ischemic preconditioning (RIPC) has demonstrated protective effects in patients with lower extremity arterial disease (LEAD) undergoing digital subtraction angiography (DSA) and/or percutaneous transluminal angioplasty (PTA). This study aimed to investigate the impact of RIPC on the metabolomical profile of LEAD patients undergoing these procedures and to elucidate its potential underlying mechanisms. A total of 100 LEAD patients were enrolled and randomly assigned to either the RIPC group (n = 46) or the sham group (n = 54). Blood samples were drawn before and 24 h after intervention. Targeted metabolomics analysis was performed using the AbsoluteIDQ p180 Kit, and changes in metabolite concentrations were compared between the groups. The RIPC group demonstrated significantly different dynamics in nine metabolites compared to the sham group, which generally showed a decrease in metabolite concentrations. The impacted metabolites included glutamate, taurine, the arginine-dimethyl-amide-to-arginine ratio, lysoPC a C24:0, lysoPC a C28:0, lysoPC a C26:1, PC aa C38:1, PC ae C30:2, and PC ae C44:3. RIPC exhibited a 'stabilization' effect, maintaining metabolite levels amidst ischemia-reperfusion injuries, suggesting its role in enhancing metabolic control. This may improve outcomes for LEAD patients. However, additional studies are needed to definitively establish causal relationships among these metabolic changes.

Sex-specific outcomes of diabetic patients with acute myocardial infarction who have undergone percutaneous coronary intervention: a register linkage study.

BACKGROUND: The presence of diabetes mellitus poses a challenge in the treatment of patients with acute myocardial infarction (AMI). We aimed to evaluate the sex-specific outcomes of diabetic and non-diabetic patients with AMI who have undergone percutaneous coronary intervention (PCI). METHODS: Data of the Estonian Myocardial Infarction Registry for years 2006-2009 were linked with the Health Insurance Fund database and the Population Registry. Hazard ratios (HRs) with the 95% confidence intervals (CIs) for the primary composite outcome (non-fatal AMI, revascularization, or death whichever occurred first) and for the secondary outcome (all cause mortality) were calculated comparing diabetic with non-diabetic patients by sex. RESULTS: In the final study population (n=1652), 14.6% of the men and 24.0% of the women had diabetes. Overall, the diabetics had higher rates of cardiovascular risk factors, co-morbidities, and 3-4 vessel disease among both men and women (p<0.01). Among women, the diabetic patients were younger, they presented later and less often with typical symptoms of chest pain than the non-diabetics (p<0.01). Women with diabetes received aspirin and reperfusion for ST-segment elevation AMI less often than those without diabetes (p<0.01). During a follow-up of over two years, in multivariate analysis, diabetes was associated with worse outcomes only in women: the adjusted HR for the primary outcome 1.44 (95% CI 1.05-1.96) and for the secondary outcome 1.83 (95% CI 1.17-2.89). These results were largely driven by a high (12.0%) mortality during hospitalization of diabetic women. CONCLUSIONS: Diabetic women with AMI who have undergone PCI are a high-risk group warranting special attention in treatment strategies, especially during hospitalization. There is a need to improve the expertise to detect AMI earlier, decrease disparities in management, and find targeted PCI strategies with adjunctive antithrombotic regimes in women with diabetes.

Effect of vitamin D on aortic remodeling in streptozotocin-induced diabetes.

BACKGROUND: Diabetes mellitus is associated with micro- and macrovascular complications and increased cardiovascular risk. Elevated levels of serum asymmetric dimethylarginine (ADMA) may be responsible for endothelial dysfunction associated with diabetes-induced vascular impairment. Vitamin D may have potential protective effects against arterial stiffening. This study aimed to examine both the effects of diabetes on the functional/structural properties of the aorta and the endothelial function and the effects of vitamin D supplementation. METHODS: Male Wistar rats (n = 30) were randomly assigned to control untreated, diabetic untreated, and diabetic + cholecalciferol groups. Diabetes was induced by intraperitoneal injection of streptozotocin, followed by oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment group. Aortic pulse wave velocity (PWV) was recorded over a mean arterial pressure (MAP) range of 50 to 200 mmHg using a dual pressure sensor catheter. Intravenous infusion of phenylephrine and nitroglycerine was used to increase and decrease MAP, respectively. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a radioimmune assay. ADMA levels in serum were measured by enzyme-linked immunoassay. Aortic samples were collected for histomorphometrical analysis. RESULTS: PWV up to MAP 170 mmHg did not reveal any significant differences between all groups, but in diabetic rats, PWV was significantly elevated across MAP range between 170 and 200 mmHg. Isobaric PWV was similar between the treated and untreated diabetic groups, despite significant differences in the levels of serum 25(OH)D (493 ± 125 nmol/L vs 108 ± 38 nmol/L, respectively). Serum levels of ADMA were similarly increased in the treated and untreated diabetic groups, compared to the control group. The concentration and integrity of the elastic lamellae in the medial layer of the aorta was impaired in untreated diabetic rats and improved by vitamin D supplementation. CONCLUSION: PWV profile determined under isobaric conditions demonstrated differential effects of uncontrolled diabetes on aortic stiffness. Diabetes was also associated with elevated serum levels of ADMA. Vitamin D supplementation did not improve the functional indices of aortic stiffness or endothelial function, but prevented the fragmentation of elastic fibers in the aortic media.

Nebivolol and metoprolol: long-term effects on inflammation and oxidative stress in essential hypertension.

Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p < 0.01 and for both drugs), but only nebivolol reduced 8-isoprostanes (p = 0.01). In the metoprolol group, change in oxLDL levels correlated with change in systolic blood pressure (r = 0.45; p < 0.01) and pulse pressure (r = 0.47; p < 0.01). Both metoprolol and nebivolol reduced ICAM-1 (p < 0.01). There was no change in IL-6, hsCRP, fibrinogen, or ADMA levels in either group. These data suggest that in long-term antihypertensive treatment both the cardioselective beta blocker metoprolol succinate and the vasodilating beta blocker nebivolol have inflammation-related effects but only nebivolol has a favourable blood pressure-independent effect on oxidative stress.

Markers of Inflammation, Oxidative Stress, and Fibrosis in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinical practice. The pathogenesis of AF is linked to inflammatory reaction and oxidative stress, which leads to fibrosis of the atria and progression of the disease. The purpose of this study was to define the role of several biomarkers of inflammation, fibrosis, and oxidative stress (OxS). We included 75 patients with paroxysmal/persistent AF, who were admitted for electrical cardioversion or pulmonary vein isolation (PVI). High-sensitivity C-reactive protein (hsCRP), galectin-3 (Gal-3), myeloperoxidase (MPO), oxidized low-density lipoprotein (oxLDL), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before the procedures. We compared the results with those of 75 healthy age-, sex-, and blood pressure-matched individuals. The patients were followed up for 1 year after the intervention to establish the recurrence of AF and its association with the measured markers. Patients with AF had higher MPO (52.6 vs. 36.2 ng/ml, p < 0.001) and NT-proBNP (209.0 vs. 28.0 pg/ml, p < 0.001) compared to healthy subjects. Also, they showed significantly higher levels of hsCRP (1.5 vs. 1.1 mg/l, p = 0.001) and Gal-3 (11.4 vs. 9.7 mg/l, p = 0.003), while there was no difference found in oxLDL (71.5 vs. 71.7 U/l, p = 0.449). MPO (OR = 1.012, p = 0.014), hsCRP (OR = 1.265, p = 0.026), and weight (OR = 1.029, p = 0.013) were independently associated with AF in a multivariable logistic regression analysis. Patients with successful maintenance of sinus rhythm (SR) for one year had lower baseline MPO (40.5 vs. 84.3 ng/ml, p = 0.005) and NT-proBNP (127.5 vs. 694.0 pg/ml, p < 0.001) compared to patients with recurrent AF episodes, but there was no difference in hsCRP, Gal-3, or oxLDL between them. MPO (OR = 0.985, p = 0.010) was independently associated with AF recurrence during the follow-up period when adjusted for cofounders. Patients with AF had increased markers of inflammation and fibrosis, while there was no increase detected in the OxS marker oxLDL. MPO was independently associated with AF in a multivariate model. Inflammatory and fibrotic mechanisms are important factors in electrical and structural remodelling progress in the atria of patients with AF.

Effects of RIPC on the Metabolome in Patients Undergoing Vascular Surgery: A Randomized Controlled Trial.

BACKGROUND: remote ischemic preconditioning (RIPC) is a phenomenon in which short episodes of ischemia are applied to distant organs to prepare target organs for more prolonged ischemia and to induce protection against ischemia-reperfusion injury. This study aims to evaluate whether preoperatively performed RIPC affects the metabolome and to assess whether metabolomic changes correlate with heart and kidney injury markers after vascular surgery. METHODS: a randomized sham-controlled, double-blinded trial was conducted at Tartu University Hospital. Patients undergoing elective open vascular surgery were recruited and RIPC was applied before operation. Blood was collected preoperatively and 24 h postoperatively. The metabolome was analyzed using the AbsoluteIDQ p180 Kit. RESULTS: final analysis included 45 patients from the RIPC group and 47 from the sham group. RIPC did not significantly alter metabolites 24 h postoperatively. There was positive correlation of change in the kynurenine/tryptophan ratio with change in hs-troponin T (r = 0.570, p < 0.001), NT-proBNP (r = 0.552, p < 0.001), cystatin C (r = 0.534, p < 0.001) and beta-2-microglobulin (r = 0.504, p < 0.001) only in the RIPC group. CONCLUSIONS: preoperative RIPC did not significantly affect the metabolome 24 h after vascular surgery. The positive linear correlation of kynurenine/tryptophan ratio with heart and kidney injury markers suggests that the kynurenine-tryptophan pathway can play a role in RIPC-associated cardio- and nephroprotective effects.

Comparison of management and outcomes of ST-segment elevation myocardial infarction patients in Estonia, Hungary, Norway, and Sweden according to national ongoing registries.

AIMS: Describe the characteristics, management and outcomes of hospitalized ST-segment elevation myocardial infarction (STEMI) patients according to national ongoing myocardial infarction registries in Estonia, Hungary, Norway, and Sweden. METHODS AND RESULTS: Country-level aggregated data was used to study baseline characteristics, use of in-hospital procedures, medications at discharge, in-hospital complications, 30-day and 1-year mortality for all patients admitted with STEMI during 2014-2017 using data from EMIR (Estonia; n = 4584), HUMIR (Hungary; n = 23 685), NORMI (Norway; n = 12 414, data for 2013-2016), and SWEDEHEART (Sweden; n = 23 342). Estonia and Hungary had a higher proportion of women, patients with hypertension, diabetes, and peripheral artery disease compared to Norway and Sweden. Rates of reperfusion varied from 75.7% in Estonia to 84.0% in Sweden. Rates of recommendation of discharge medications were generally high and similar. However, Estonia demonstrated the lowest rates of dual antiplatelet therapy (78.1%) and statins (86.5%). Norway had the lowest rates of beta-blockers (80.5%) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (61.5%). The 30-day mortality rates ranged between 9.9% and 13.4% remaining lowest in Sweden. One-year mortality rates ranged from 14.8% in Sweden and 16.0% in Norway to 20.6% in Hungary and 21.1% in Estonia. Age-adjusted lethality rates were highest for Hungary and lowest for Sweden. CONCLUSION: This inter-country comparison of data from four national ongoing European registries provides new insights into the risk factors, management and outcomes of patients with STEMI. There are several possible reasons for the findings, including coverage of the registries and variability of baseline-characteristics' definitions that need to be further explored.