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.

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.

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.

Sex-related differences in the management and outcomes of patients hospitalized with ST-elevation myocardial infarction: a comparison within four European myocardial infarction registries.

Aims: Data on how differences in risk factors, treatments, and outcomes differ between sexes in European countries are scarce. We aimed to study sex-related differences regarding baseline characteristics, in-hospital managements, and mortality of ST-elevation myocardial infarction (STEMI) patients in different European countries. Methods and results: Patients over the age of 18 with STEMI who were treated in hospitals in 2014-17 and registered in one of the national myocardial infarction registers in Estonia (n = 5817), Hungary (n = 30 787), Norway (n = 33 054), and Sweden (n = 49 533) were included. Cardiovascular risk factors, hospital treatment, and recommendation of discharge medications were obtained from the infarction registries. The primary outcome was mortality, in-hospital, after 30 days and after 1 year. Logistic and cox regression models were used to study the associations of sex and outcomes in the respective countries. Women were older than men (70-78 and 62-68 years, respectively) and received coronary angiography, percutaneous coronary intervention, left ventricular ejection fraction assessment, and evidence-based drugs to a lesser extent than men, in all countries. The crude mortality in-hospital rates (10.9-15.9 and 6.5-8.9%, respectively) at 30 days (13.0-19.9 and 8.2-10.9%, respectively) and at 1 year (20.3-28.1 and 12.4-17.2%, respectively) after hospitalization were higher in women than in men. In all countries, the sex-specific differences in mortality were attenuated in the adjusted analysis for 1-year mortality. Conclusion: Despite improved awareness of the sex-specific inequalities on managing patients with acute myocardial infarction in Europe, country-level data from this study show that women still receive less guideline-recommended management.

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.

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.

Differences in characteristics, treatments and outcomes in patients with non-ST-elevation myocardial infarction: novel insights from four national European continuous real-world registries.

AIMS: To study baseline characteristics, in-hospital managements and mortality of non-ST-elevation myocardial infarction (NSTEMI) patients in different European countries. METHODS AND RESULTS: NSTEMI patients enrolled in the national myocardial infarction (MI) registries [EMIR; n = 5817 (Estonia), HUMIR; n = 30 787 (Hungary), NORMI; n = 33 054 (Norway), and SWEDEHEART; n = 49 533 (Sweden)] from 2014 to 2017 were included and presented as aggregated data. The median age at admission ranged from 70 to 75 years. Current smoking status was numerically higher in Norway (24%), Estonia (22%), and Hungary (19%), as compared to Sweden (17%). Patients in Hungary had a high rate of diabetes mellitus (37%) and hypertension (84%). The proportion of performed coronary angiographies (58% vs. 75%) and percutaneous coronary interventions (38% vs. 56%), differed most between Norway and Hungary. Prescription of dual antiplatelet therapy at hospital discharge ranged from 60% (Estonia) to 81% (Hungary). In-hospital death ranged from 3.5% (Sweden) to 9% (Estonia). The crude mortality rate at 1 month was 12% in Norway and 5% in Sweden (5%), whereas the 1-year mortality rates were similar (20-23%) in Hungary, Estonia, and Norway and 15% in Sweden. CONCLUSION: Cross-comparisons of four national European MI registries provide important data on differences in risk factors and treatment regiments that may explain some of the observed differences in death rates. A unified European continuous MI registry could be an option to better understand how implementation of guideline-recommended therapy can be used to reduce the burden of cardiovascular disease.

The Role of RIPC in Preventing Organ Damage, Inflammation, and Oxidative Stress during Lower Limb DSA: A Randomised Controlled Trial.

OBJECTIVE: Diagnostic digital subtraction angiography (DSA) and DSA with percutaneous transluminal angioplasty (DSA-PTA) are common procedures for diagnosing and treating symptomatic lower extremity arterial disease (LEAD). However, organ damage following DSA and DSA-PTA is often underrecognised and hence undiagnosed. To reduce the risk induced by invasive procedures in symptomatic LEAD patients, the method of remote ischemic preconditioning (RIPC) has been suggested. The aim of the current study was to assess the effect of RIPC intervention on the organ damage markers profile, oxidative stress, and inflammation biomarkers in LEAD patients undergoing DSA and DSA-PTA procedure. METHODS: The RIPC intervention was performed by inflating a standard blood pressure cuff on the patient's upper arm to 200 mmHg for 5 minutes four times with 5-minute perfusion between each cycle. The sham intervention was performed similarly, but the cuff was inflated to 20 mmHg. Changes in the cardiac and renal damage biomarkers' profile, oxidative stress, and inflammation biomarkers were recorded before and 24 hours after DSA or DSA-PTA. RESULTS: A total of 111 (RIPC 54, sham 57) patients with symptomatic LEAD scheduled for endovascular procedure were randomised, and 102 patients (RIPC 47, sham 55) completed the study protocol. RIPC significantly limited the increase of adiponectine levels after DSA and DSA-PTA, compared to sham intervention (p = 0.020), but CK-MB levels were markedly lower in the sham group (p = 0.047) after procedure. There was no significant difference between the RIPC and the sham group in mean changes in hs-troponin-T (p = 0.25), NT-proBNP (p = 0.24), creatinine (p = 0.76), eGFR (p = 0.61), urea (p = 0.95), beta-2-microglobuline (p = 0.34), or cystatine C (p = 0.24) levels. CONCLUSION: In this controlled clinical study, RIPC failed to improve the profile of renal and cardiac biomarkers in patients with LEAD periprocedurally. RIPC significantly limits the rise in adiponectin levels and may influence the decrease of CK-MB levels 24 hours after endovascular procedure.

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.

Atrial fibrillation is associated with increased central blood pressure and arterial stiffness.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and beta blockers (BBs) are the drugs of choice for rate or rhythm control in these patients. The purpose of this study was to describe differences in arterial stiffness (AS), central blood pressure (cBP), and the role of BBs on cBP in patients with AF compared to healthy individuals. The authors included 76 patients with paroxysmal/persistent AF. Carotid-femoral pulse wave velocity (PWV) and cBP were measured and compared with data from 75 healthy individuals. Patients with AF had higher PWV (8.0 m/s vs. 7.2 m/s, p < .001), central systolic blood pressure (cSBP) (118 mm Hg vs. 114 mm Hg, p = .033), central pulse pressure (cPP) (39 mm Hg vs. 37 mm Hg, p = .035) and lower pulse pressure amplification (PPA) (1.24 vs. 1.30, p = .015), without differences in peripheral blood pressure (pBP) and heart rate (HR). AF patients had significantly increased PWV (ß= 0.500, p = .010, adjusted R² = 0.37) after adjustment for confounding factors. The use of BBs significantly reduced PPA (ß = -0.059, p = .017, adjusted R² = 0.30). AF patients have higher PWV, cSBP, cPP, and lower PPA, compared to healthy patients. These findings support the role of AS in the development of AF. Use of BBs is related to a potential adverse effect on cBP.

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 influences the levels of acylcarnitines in vascular surgery: a randomised clinical trial.

BACKGROUND: Vascular surgery patients have reduced tissues` blood supply, which may lead to mitochondrial dysfunction and accumulation of acylcarnitines (ACs). It has been suggested that remote ischaemic preconditioning (RIPC) has its organ protective effect via promoting mitochondrial function. The aim of this study was to evaluate the effect of RIPC on the profile of ACs in the vascular surgery patients. METHODS: This is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open surgical repair of abdominal aortic aneurysm, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 min of ischaemia, followed by 5 min of reperfusion, was applied. A blood pressure cuff was used for RIPC or a sham procedure. Blood was collected preoperatively and approximately 24 h postoperatively. The profile of ACs was analysed using the AbsoluteIDQp180 kit (Biocrates Life Sciences AG, Innsbruck, Austria). RESULTS: Ninety-eight patients were recruited and randomised into the study groups and 45 patients from the RIPC group and 47 patients from the sham group were included in final analysis. There was a statistically significant difference between the groups regarding the changes in C3-OH (p = 0.023)-there was a decrease (- 0.007 µmol/L, ± 0.020 µmol/L, p = 0.0233) in the RIPC group and increase (0.002 µmol/L, ± 0.015 µmol/L, p = 0.481) in the sham group. Additionally, a decrease from baseline to 24 h after surgery (p < 0.05) was detected both in the sham and the RIPC group in the levels of following ACs: C2, C8, C10, C10:1, C12, C12:1, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2. In the sham group, there was an increase (p < 0.05) in the levels of C0 (carnitine) and a decrease in the level of C18:1-OH. In the RIPC group, a decrease (p < 0.05) was noted in the levels of C3-OH, C3-DC (C4-OH), C6:1, C9, C10:2. CONCLUSIONS: It can be concluded that RIPC may have an effect on the levels of ACs and might therefore have protective effects on mitochondria in the vascular surgery patients. Further larger studies conducted on homogenous populations are needed to make more definite conclusions about the effect of RIPC on the metabolism of ACs. TRIAL REGISTRATION: ClinicalTrials.gov database, NCT02689414. Registered 24 February 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02689414.

Atenolol's Inferior Ability to Reduce Central vs Peripheral Blood Pressure Can Be Explained by the Combination of Its Heart Rate-Dependent and Heart Rate-Independent Effects.

OBJECTIVE: Whether the inferior ability of atenolol to reduce central (aortic) compared to peripheral (brachial) blood pressure (BP) is related to its heart rate (HR)-dependent or -independent effects, or their combination, remains unclear. To provide further mechanistic insight into this topic, we studied the acute effects of atenolol versus nebivolol and ivabradine on systolic blood pressure amplification (SBPA; peripheral systolic BP minus central systolic BP) in a model of sick sinus syndrome patients with a permanent dual-chamber cardiac pacemaker in a nonrandomized single-blind single-group clinical trial. METHODS: We determined hemodynamic indices noninvasively (Sphygmocor XCEL) before and at least 3 h after administration of oral atenolol 50 or 100 mg, nebivolol 5 mg, or ivabradine 5 or 7.5 mg during atrial pacing at a low (40 bpm), middle (60 bpm), and high (90 bpm) HR level in 25 participants (mean age 65.5 years, 12 men). RESULTS: At the low HR level, i.e., when the drugs could exert their HR-dependent and HR-independent effects on central BP, only atenolol produced a significant decrease in SBPA (mean change 0.74 ± 1.58 mmHg (95% CI, 0.09-1.40; P = 0.028)), indicating inferior central vs peripheral systolic BP change. However, we observed no significant change in SBPA with atenolol at the middle and high HR levels, i.e., when HR-dependent mechanisms had been eliminated by pacing. CONCLUSION: The findings of our trial with a mechanistic approach to the topic imply that the inferior ability of atenolol to reduce central vs peripheral BP can be explained by the combination of its heart rate-dependent and -independent effects. This trial is registered with NCT03245996.

Remote Ischaemic Preconditioning Reduces Kidney Injury Biomarkers in Patients Undergoing Open Surgical Lower Limb Revascularisation: A Randomised Trial.

BACKGROUND AND AIMS: Perioperative kidney injury affects 12.7% of patients undergoing lower limb revascularisation surgery. Remote ischaemic preconditioning (RIPC) is a potentially protective procedure against organ damage and consists of short nonlethal episodes of ischaemia. The main objective of this substudy was to evaluate the effect of RIPC on kidney function, inflammation, and oxidative stress in patients undergoing open surgical lower limb revascularisation. Materials and Methods. This is a subgroup analysis of a randomised, sham-controlled, double-blinded, single-centre study. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia in patients undergoing open surgical lower limb revascularisation. The RIPC protocol consisted of 4 cycles of 5 minutes of ischaemia, with 5 minutes of reperfusion between every episode. Blood was collected for analysis preoperatively, 2, 8, and 24 hours after surgery, and urine was collected preoperatively and 24 hours after surgery. RESULTS: Data of 56 patients were included in the analysis. Serum creatinine, cystatin C, and beta-2 microglobulin increased, and eGFR decreased across all time points significantly more in the sham group than in the RIPC group (p = 0.021, p = 0.021, p = 0.021, p = 0.021, p = 0.021. CONCLUSIONS: Our finding of reduced release of kidney injury biomarkers may indicate the renoprotective effect of RIPC in patients undergoing open surgical lower limb revascularisation. The trial is registered with ClinicalTrials.gov NCT02689414.

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.

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.

Estimating the performance of three cardiovascular disease risk scores: the Estonian Biobank cohort study.

BACKGROUND: We aim to investigate the predictive ability of PCE (Pooled Cohort Equations), QRISK2 and SCORE (Systematic COronary Risk Estimation) scoring systems for atherosclerotic cardiovascular disease (ASCVD) risk prediction in Estonia, a country with one of the highest ASCVD event rates in Europe. METHODS: Seven-year risk estimates were calculated in risk score-specific subsets of the Estonian Biobank cohort. Calibration was assessed by standardised incidence ratios (SIRs) and discrimination by Harrell's C-statistics. In addition, a head-to-head comparison of the scores was performed in the intersection of the three score-specific subcohorts. RESULTS: PCE, QRISK2 and SCORE risk estimates were calculated for 4356, 7191 and 3987 eligible individuals, respectively. During the 7-year follow-up, 220 hard ASCVD events (PCE outcome), 671 ASCVD events (QRISK2 outcome) and 94 ASCVD deaths (SCORE outcome) occurred among the score-specific subsets of the cohort. While PCE (SIR 1.03, 95% CI 0.90 to 1.18) and SCORE (SIR 0.99, 95% CI 0.81 to 1.21) were calibrated well for the cohort, QRISK2 underestimated the risk by 48% (SIR 0.52, 95% CI 0.48 to 0.56). In terms of discrimination, PCE (C-statistic 0.778) was inferior to QRISK2 (C-statistic 0.812) and SCORE (C-statistic 0.865). All three risk scores performed at similar level in the head-to-head comparison. CONCLUSION: Of three widely used ASCVD risk scores, PCE and SCORE performed at acceptable level, while QRISK2 underestimated ASCVD risk markedly. These results highlight the need for evaluating the accuracy of ASCVD risk scores prior to use in high-risk populations.

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.