Cerebro-cardiovascular Events Research Articles

Physiological Targets for Orthostatic Hypotension: Improving Nonpharmacological Interventions in Patients with Orthostatic Cerebral Hypoperfusion.

Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBFv) during orthostatic stress are associated with a decrease in end-tidal CO2 (EtCO2) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO2 and cerebral hypoperfusion in patients (N = 72) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBFv during HUT was associated with a larger reduction in ETCO2 and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO2 was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO2 should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.

Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials

BackgroundWe report long-term, end-of-study program safety outcomes from 25 randomized clinical trials (RCTs) in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) [including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] who received ≥ 1 dose of Ixekizumab (IXE) over 5 years (PsO) or up to 3 years (PsA, axSpA).MethodsThis integrated safety analysis consists of data from patients who received any dose of IXE, across 25 RCTs (17 PsO, 4 PsA, 4 axSpA). Rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and selected adverse events (AEs) of interest were analyzed for all pooled studies by years of therapy and overall, through March 2022. Results were reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) overall and at successive year intervals.ResultsSix thousand eight hundred ninety two adult patients with PsO, 1401 with PsA, and 932 with axSpA (including AS and nr-axSpA), with a cumulative IXE exposure of 22,371.1 PY were included. The most commonly reported TEAE across indications was nasopharyngitis (IRs per 100 PY: 8.8 (PsO), 9.0 (PsA), 8.4 (axSpA)). SAEs were reported by 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8). Forty-five deaths were reported (PsO, n = 36, IR 0.2; PsA, n = 6, IR 0.3; axSpA, n = 3, IR 0.1). TEAEs did not increase during IXE exposure: IRs per 100 PY, PsO: 88.9 to 63.2 (year 0–1 to 4–5), PsA: 87 to 67.3 (year 0–1 to 2–3), axSpA: 82.1 to 55.4 (year 0–1 to > = 2). IRs per 100 PY of discontinuation from IXE due to AE were 2.9 (PsO), 5.1 (PsA), and 3.1 (axSpA). IRs per 100 PY of injection site reactions were 5.9 (PsO), 11.6 (PsA) and 7.4 (axSpA); Candida: 1.9 (PsO), 2.0 (PsA), and 1.2 (axSpA); depression, major adverse cerebro-cardiovascular events and malignancies: ≤ 1.6 across all indications. Adjudicated IRs per 100 PY of inflammatory bowel disease were ≤ 0.8 across indications (0.1 [PsO]; 0.1 [PsA]; 0.8 [axSpA]).ConclusionsIn this integrated safety analysis, consisting of over 22,000 PY of exposure, the long-term safety profile of IXE was found to be consistent with previous, earlier reports, with no new safety signals identified.Trial registrationNCT registration numbers for RCTs included in this integrated analysis can be found in Additional File 1.

Impact of Comorbid Sleep-Disordered Breathing and Atrial Fibrillation on the Long-Term Outcome After Ischemic Stroke.

Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke. In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events. Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36]). Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.

Blood pressure variability, nocturnal heart rate variability and endothelial function predict recurrent cerebro-cardiovascular events following ischemic stroke.

Cardiovascular parameters characterizing blood pressure (BP), heart rate (HR), endothelial function and arterial stiffness predict cerebro-cardiovascular events (CCVE) in the general population. Considering the paucity of data in stroke patients, we assessed these parameters as potential predictors of recurrent CCVE at acute stroke stroke. This is a secondary outcome analysis of a prospective observational longitudinal Sleep Deficiency & Stroke Outcome Study (ClinicalTrials.gov Identifier: NCT02559739). The study consecutively recruited acute ischemic stroke patients. Cardiovascular parameters (blood pressure variability [BPV], heart rate variability [HRV], endothelial function, and arterial stiffness) were assessed within the first week post-stroke. Future CCVE were recorded over a 3-year follow-up. Multivariate Cox regression analysis was used to investigate the prognostic value of 48 cardiovascular parameters regarding CCVE risk. Out of 447 recruited patients, 359 were included in this analysis. 20% of patients developed a future CCVE. A high variability of systolic BP (n = 333) and nocturnal HR (non-linear parameters; n = 187) at acute stroke predicted CCVE risk after adjustment for demographic parameters, cardiovascular risk factors and mean BP or HR, respectively. Endothelial dysfunction (n = 105) at acute stroke predicted CCVE risk after adjustment for age and sex, but not after adjustment for cardiovascular risk factors. Diurnal HR and arterial stiffness at acute stroke were not associated with CCVE risk. High blood pressure variability, high nocturnal HRV and endothelial function contribute to the risk for future CCVE after stroke.

Brain Derived Neurotrophic Factor Methylation and Long-term Outcomes after Stroke Interacting with Suicidal Ideation.

This study aimed to evaluate the unexplored relationship between BDNF methylation, long-term outcomes, and its interaction with suicidal ideation (SI), which is closely associated with both BDNF expression and stroke outcomes. A total of 278 stroke patients were assessed for BDNF methylation status and SI using suicide-related item in the Montgomery-Åsberg Depression Rating Scale at 2 weeks post-stroke. We investigated the incidence of composite cerebro-cardiovascular events (CCVEs) during an 8-14-year period after the initial stroke as long-term stroke outcome. We conducted Cox regression models adjusted for covariates to evaluate the association between BDNF methylation status and CCVEs, as well as its interaction with post-stroke SI at 2 weeks. Higher methylation status of CpG 1, 3, and 5, but not the average value, predicted a greater number of composite CCVEs during 8-14 years following the stroke. The associations between a higher methylation status of CpGs 1, 3, 5, and 8, as well as the average BDNF methylation value, and a greater number of composite CCVEs, were prominent in patients who had post-stroke SI at 2 weeks. Notably, a significant interaction between methylation status and SI on composite CCVEs was observed only for CpG 8. The significant association between BDNF methylation and poor long-term stroke outcomes, particularly amplified in individuals who had post-stroke SI at 2 weeks, suggested that evaluating the biological marker status of BDNF methylation along with assessing SI during the acute phase of stroke can help predict long-term outcomes.

Impact of atrial fibrillation on cerebro-cardiovascular outcome of heart failure with mildly-reduced ejection fraction.

Atrial fibrillation (AF) and heart failure (HF) often co-exist and are closely intertwined. The impact of AF on the outcome of patients with heart failure with mildly-reduced ejection fraction (HFmrEF) is not fully clear. This study aimed to investigate the impact of AF on the outcomes of hospitalized HFmrEF patients. The study included 1691 consecutive patients with HFmrEF (mean 68.2years, 64.8% male) including 296 AF patients. Patients completed 1year and mean of 33month clinical follow-up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was cerebro-cardiovascular events (CCE, composite of HF rehospitalization, stroke, or cardiovascular death). After propensity score matching, 296 patients were included into the AF group (mean 71.5years) and 592 patients into the non-AF group (mean 70.6years). After propensity score matching, CCE at 1year (59.1% vs. 48.5%, P=0.003) and at a mean of 33month (77.0% vs. 70.6%, P=0.043). AF was independently associated with increased CCE within 1year (HR=1.31, 95% CI 1.07 to 1.61, P=0.010) and at 33months (HR=1.20, 95% CI 1.00 to 1.43, P=0.050) post-discharge after adjusted for other clinical confounders including discharge heart rate, NT-proBNP, haemoglobin, and uric acid. AF is independently associated with an increased risk of CCE in HFmrEF patients within 1year and at a mean of 33months after discharge.

Lean nonalcoholic fatty liver disease: Age-dependent differences in pathology, prognosis, and liver-related events.

This study aimed to evaluate the age-specific characteristics, prognosis, and complications of patients with lean nonalcoholic fatty liver disease (NAFLD). Background factors (age, sex, diabetes, dyslipidemia, hypertension, and PNPLA3 gene polymorphism), blood test results, liver histology findings, muscle mass, and grip strength were investigated in 782 patients with NAFLD who underwent liver biopsy. Prognosis and complications were compared among 549 patients with nonlean or lean NAFLD who were followed up for 6.5years. Additionally, background factors, blood test results, liver histology findings, prognosis, and complications were compared according to age (≥60years vs. <60years) in patients with lean NAFLD. Lean NAFLD patients showed lower aspartate aminotransferase, alanine aminotransferase, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein, ferritin, and leptin but higher adiponectin and hemoglobin A1c (HbA1c) levels than patients with nonlean NAFLD. Furthermore, lean NAFLD patients showed less liver fibrosis, inflammation, steatosis, and ballooning. Among lean NAFLD patients, those aged 60years and older were more frequently female, showed higher rates of hypertension, diabetes, and dyslipidemia, had higher HbA1c and type IV collagen 7S levels, lower platelet count, higher liver fibrosis and inflammation grades, and lower muscle mass and grip strength. Lean NAFLD was associated with a worse prognosis in patients aged 60years and over than in those younger than 60years of age and with a higher incidence of liver-related disease, cerebrocardiovascular events, and nonliver cancer. Age is an important consideration in patients with lean NAFLD. Compared with nonlean NAFLD, lean NAFLD was associated with a worse prognosis and higher risk of complications in patients aged 60years and older.

P186 Long-term safety of ixekizumab in adult patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis

P186 Long-term safety of ixekizumab in adult patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis

EFFECT OF ASPIRIN IN COVID-19 OUTCOMES OF OLDER ADULTS WITH A HISTORY OF CORONARY ARTERY DISEASE

Abstract Background Advanced age and coronary artery disease (CAD) have been associated with a dismal prognosis in patients infected with COVID-19, most likely due to the virus’s thrombogenic effects. Older adults with a history of CAD have routinely used low-dose Aspirin (LDA) as prevention due to their increased risk of cerebro-cardiovascular events. However, it is unclear if this population would benefit from LDA when infected with COVID-19. Methods A retrospective study was conducted using the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). Using ICD codes, patients aged 65–75 and Elixhauser Comorbidity Score(ECI)&amp;gt;4 with a history of CAD admitted for COVID-19 were identified. The use of LDA for 1 month before the index event was used to split the cohort into two matched groups by age, gender, ECI, and other cardiovascular diseases. Records of groups were reviewed for multiple outcomes 30 days after admission. Pearson’s chi-squared test was used to compare groups. The strength of association was reported as Risk Ratios (RR). Results 4,017 patients with no difference in the mean age, gender, and ECI were included in each group. No differences present in 30-days all-cause readmission(RR=1.04, CI95% =0.92–1.17, p=0.49), mortality(RR=0.63, CI95%=0.30–1.29, p=0.28), ICU admission(RR=1.01, CI95%=0.89–1.15, p=0.79), gastrointestinal bleeding(RR=1.09, CI95% = 0.85–1.40, p=0.51), and intracranial hemorrhage(RR=0.69, CI95%=0.26–1.83, p=0.62) between groups. Conclusion LDA didn’t improve the evaluated outcomes in older persons 30 days after admission. A plausible explanation is that COVID-19’s thrombogenic mechanism is likely atypical.

The relationship of α-hydroxybutyrate dehydrogenase with 1-year outcomes in patients with intracerebral hemorrhage: A retrospective study.

Cardiac enzymes are recognized as a valuable tool for predicting the prognosis of various cardiovascular diseases. The prognostic value of alpha-hydroxybutyrate dehydrogenase (α-HBDH) in patients with intracerebral hemorrhage (ICH) was ambiguous and not evaluated. Two hundred and thirteen Chinese patients with ICH participated in the study from December 2018 to December 2019. Laboratory routine tests and cardiac enzymes, including α-HBDH level, were examined and analyzed. All the patients were classified into two groups by the median value of α-HBDH: B1 <175.90 and B2 ≥175.90 U/L. The clinical outcomes included functional outcome (according to modified Rankin Scale (mRS) score ≥3), all-cause death, and recurrent cerebro-cardiovascular events 1 year after discharge. Associations between the α-HBDH and the outcomes were evaluated using logistic regression analysis. Univariate survival analysis was performed by the Kaplan-Meier method and log-rank test. Of the 213 patients, 117 had α-HBDH ≥175.90 U/L. Eighty-two patients had poor functional outcomes (mRS≥3). During the 1-year follow-up, a total of 20 patients died, and 15 of them had α-HBDH ≥175.90 U/L during the follow-up time. Moreover, 24 recurrent events were recorded. After adjusting confounding factors, α-HBDH (≥175.90) remained an indicator of poor outcome (mRS 3-6), all-cause death, and recurrent cerebro-cardiovascular events. The ORs for B2 vs. B1 were 4.78 (95% CI: 2.60 to 8.78, P = 0.001), 2.63 (95% CI: 0.80 to 8.59, P = 0.11), and 2.40 (95% CI: 0.82 to 7.02, P = 0.11) for poor functional outcomes with mRS ≥ 3, all-cause death, and recurrent cerebro-cardiovascular events, respectively. Increased α-HBDH at admission was independently related to poor functional outcome and all-cause mortality in patients with ICH at 1-year follow-up.

Prevalence and Clinical Impact of Electrocardiographic Abnormalities in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is a strong risk factor for cardiovascular disease. An electrocardiogram (ECG) is a basic test for screening cardiovascular disease. However, the impact of ECG abnormalities on cardiovascular prognosis in patients with CKD is largely unknown. A total of 2442 patients with CKD (stages 3–5) who underwent ECG between 2013 and 2015 were selected from the electronic health record database of the Korea University Anam Hospital. ECG abnormalities were defined using the Minnesota classification. The five-year major adverse cerebrocardiovascular event (MACCE), the composite of death, myocardial infarction (MI), and stroke were analyzed. The five-year incidences for MACCE were 27.7%, 20.8%, and 17.2% in patients with no, minor, and major ECG abnormality (p < 0.01). Kaplan–Meier curves also showed the highest incidence of MI, death, and MACCE in patients with major ECG abnormality. Multivariable Cox regression analysis revealed age, sex, diabetes, CKD stage, hsCRP, antipsychotic use, and major ECG abnormality as independent risk predictors for MACCE (adjusted HR of major ECG abnormality: 1.39, 95% CI: 1.09–1.76, p < 01). Among the detailed ECG diagnoses, sinus tachycardia, myocardial ischemia, atrial premature complex, and right axis deviation were proposed as important ECG diagnoses. The accuracy of cardiovascular risk stratification was improved when the ECG results were added to the conventional SCORE model (net reclassification index 0.07). ECG helps to predict future cerebrocardiovascular events in CKD patients. ECG diagnosis can be useful for cardiovascular risk evaluation in CKD patients when applied in addition to the conventional risk stratification model.

Outcome of Percutaneous Coronary Intervention in Old Patients Presenting with Acute Coronary Syndrome.

Octogenarians (age≥80 years) with coronary artery disease constitute a high-risk group and the elderly undergoing percutaneous coronary intervention (PCI) are at higher risk of adverse outcomes compared to young patients. In this study, we aimed to describe the outcomes of the elderly with acute coronary syndrome (ACS) who underwent PCI and also to identify the predictors of short-term major adverse cerebrocardiovascular events (MACCE) in octogenarians. In this registry-based cohort study, we reviewed the data of patients (aged≥65 years) who underwent PCI. Univariate Cox-regression model was used to assess the univariate effects of covariates on mortality and MACCE and multivariate Cox-regression analysis were used to discover MACCE predictors. We reviewed the data of 3332 patients (2722 elderly [65 to 79 years], and 610 octogenarians [≥80 years]). The cumulative hazard of MACCE was significantly higher in the octogenarian group compared with the younger group (P<0.001). MACCE in octogenarians presenting with ST-elevation myocardial infarction (STEMI) was significantly higher than those with non-ST-elevation myocardial infarction/Unstable angina (NSTEMI/UA) (P<0.001); however, the cumulative hazard of mortality was not significantly different between the two groups (P=0.270). Successful PCI, left main stenosis and estimated glomerular filtration rate (eGFR) were independent predictors of MACCE in octogenarians with ACS. Octogenarians undergoing PCI had a higher rate of MACCE and mortality compared with a younger population. In octogenarians, MACCE in those with STEMI was significantly higher than those with NSTEMI/UA and the mortality trend was similar; however, the 1-year trend was in favor of the STEMI subgroup.

Real-World Effectiveness of Beta-Blockers versus Other Antihypertensives in Reducing All-Cause Mortality and Cardiovascular Events.

Aim The aim of the study was to compare the effectiveness of beta-blockers with other antihypertensive classes in reducing all-cause mortality, cardiovascular-related mortality and the risk of cerebrocardiovascular events. Methods This noninterventional study was conducted within the UK Clinical Practice Research Datalink. Hypertensive patients who initiated antihypertensive monotherapy were allocated to one of five cohorts: beta-blockers; angiotensin-converting enzyme inhibitors (ACEi); angiotensin II receptor blockers (ARB); calcium channel blockers (CCB); and diuretics. Differences in outcomes were assessed using Cox proportional hazard models with competing risks. Results A total of 44,404 patients were prescribed beta-blockers (75% atenolol), 132,545 ACEi, 12,018 ARB, 91,731 CCB, and 106,547 diuretics. At baseline, patients in the beta-blocker cohort presented more frequently with angina, arrhythmia, and atrial fibrillation. The risk of all-cause mortality was lower for those treated with ACEi, ARB, and CCB, and no difference was observed compared with diuretics (adjusted hazard ratio versus beta-blockers (98.75% CI), for ACEi 0.71 (0.61, 0.83), ARB 0.67 (0.51, 0.88), CCB 0.76 (0.66, 0.88), diuretics 1.06 (0.93, 1.22)). No differences were seen in the risk of cardiovascular mortality for patients treated with beta-blockers, ARB, CCB, and diuretics, while a lower risk in patients treated with ACEi was observed (ACEi 0.63 (0.43, 0.91), ARB 0.64 (0.32, 1.28), CCB 0.71 (0.49, 1.03), diuretics 0.97 (0.69, 1.37)). Conclusions These data add to the limited pool of evidence from real-world studies exploring the effectiveness of beta-blockers versus other antihypertensive classes. Discrepancies to previously published studies might be partly explained by differences in the selected populations and in the follow-up time.

Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure

IntroductionWe report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab.MethodsLong-term safety of the IL-17A antagonist ixekizumab was assessed from 17 randomized trials. Treatment-emergent adverse events (TEAEs)-adjusted incidence rates (IRs) per 100 patient-years (PY) within 1-year time periods through 19 March 2021 were calculated for all patients treated with at least one dose of ixekizumab. Reported cases of major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated.ResultsA total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and serious adverse events (AEs) were 32.5 and 5.4. IR of discontinuation because of AE was 2.9. A total of 36 deaths were reported. IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis (TB). IR of Candida infections (IR 1.9) was low; most cases of Candida were localized, and no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity were 5.9 and 5.6, respectively. No confirmed cases of anaphylaxis were observed. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). IBD events were uncommon, although a total of 31 patients (IR 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time.ConclusionsThe long-term safety profile for ixekizumab is consistent with that previously reported in patients with psoriasis. No new or unexpected safety events were detected.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00743-9.

Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure

ObjectivesIxekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A (IL-17A), has shown significant efficacy in the treatment of psoriatic arthritis (PsA) and sustained long-term clinical response without unexpected new...

Short-Term Prognostic Factors in Hospitalized Herpes Zoster Patients and Its Associated Cerebro-Cardiovascular Events: A Nationwide Retrospective Cohort in Japan.

BackgroundShort-term mortality and incidence of cerebrovascular and cardiovascular events (C-CVE) during hospitalization of patients with severe herpes zoster (HZ) have not been sufficiently investigated. We aimed to investigate short-term prognosis and incidence of C-CVE associated with HZ in hospitalized patients.MethodsThis retrospective cohort study from April 2016 to March 2018 included HZ inpatient cases selected from the Diagnosis Procedure Combination database—a Japanese nationwide inpatient database. HZ and C-CVE were diagnosed based on the 10th revision of the International Classification of Diseases and Injuries codes. The definition of primary exposure was that treatments were initiated within 7 days of admission, and antivirals were administered for ≥7 days. Main Outcomes were in-hospital deaths and C-CVE onset after hospitalization.ResultsAmong 16,811,501 in-hospital cases registered from 1,208 hospitals, 29,054 cases with HZ were enrolled. The median age was 71.0 years, 15,202 cases (52.3%) were female, and the HZ types were the central nervous system (n=9,034), disseminated (n=3,051), and ophthalmicus (n=1,069) types. There were 301 (1.0%) in-hospital deaths and 385 (1.3%) post-hospitalization onset of C-CVE. The 30-day in-hospital survival rates with or without underlying disease were 96.8% and 98.5%, respectively. Age ≥75 years (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.55–3.05), liver cirrhosis or hepatic failure (HR, 5.93; 95% CI, 2.16–16.27), chronic kidney disease (HR, 1.82; 95% CI, 1.24–2.68), heart failure (HR, 1.65; 95% CI, 1.22–2.24), and old cerebrovascular events (HR, 1.92; 95% CI, 1.10–3.34) were associated with poor short-term prognosis. Age ≥75 years (odds ratio [OR], 1.70; 95% CI, 1.29–2.24), diabetes (OR, 1.50; 95% CI, 1.19–1.89), dyslipidemia (OR, 1.95; 95% CI, 1.51–2.51), hyperuricemia (OR, 1.63; 95% CI, 1.18–2.27), hypertension (OR, 1.76; 95% CI, 1.40–2.20), heart failure (OR, 1.84; 95% CI, 1.32–2.55), and glucocorticoid administration (OR, 1.59; 95% CI, 1.25–2.01) were associated with increased risks for in-hospital C-CVE onset.ConclusionsThe underlying diseases that could influence the short-term mortality of severe HZ were identified. Glucocorticoid is a possible risk factor for the in-hospital onset of C-CVE after severe HZ development.

Cerebro-Cardiovascular Risk, Target Organ Damage, and Treatment Outcomes in Primary Aldosteronism.

Primary aldosteronism (PA) is the most common type of endocrine hypertension, and numerous experimental and clinical evidence have verified that prolonged exposure to excess aldosterone is responsible for an increased risk of cerebro-cardiovascular events and target organ damage (TOD) in patients with PA. Therefore, focusing on restoring the toxic effects of excess aldosterone on the target organs is very important to reduce cerebro-cardiovascular events. Current evidence convincingly demonstrates that both surgical and medical treatment strategies would benefit cerebro-cardiovascular outcomes and mortality in the long term. Understanding cerebro-cardiovascular risk in PA would help clinical doctors to achieve both early diagnosis and treatment. Therefore, in this review, we will summarize the cerebro-cardiovascular risk in PA, focusing on the TOD of aldosterone, including brain, heart, vascular system, renal, adipose tissues, diabetes, and obstructive sleep apnea (OSA). Furthermore, the various treatment outcomes of adrenalectomy and medical treatment for patients with PA will also be discussed. We hope this knowledge will help improve cerebro-cardiovascular prognosis and reduce the incidence and mortality of cerebro-cardiovascular events in patients with PA.

POSA77 Radiofrequency-Based Renal Denervation for Treatment-Resistant Hypertension in Italy: A Budget Impact Analysis

Blood pressure (BP) reduction in uncontrolled hypertension (HTN) is associated with reduced risk for cerebro-cardiovascular (CV) events and end-stage renal-disease (ESRD). The safety and efficacy of catheter-based percutaneous renal denervation (RDN) for reducing BP has been demonstrated in patients with uncontrolled HTN, including so-called “treatment resistant” hypertension (trHTN)(uncontrolled BP despite prescription of ≥ 3 antihypertensive drugs). We assessed the economic impact of RDN in trHTN from the Italian healthcare (NHS) perspective, considering the potential economic benefits through avoidance of potential CV events and ESRD.

Thrombus aspiration during primary percutaneous coronary intervention: Which patients? An observational prospective study

Since the 2000s, thrombus aspiration (TA) has been widely used in the percutaneous coronary intervention (PCI) of ST elevated myocardial infarction (STEMI). Otherwise, recent trials have questioned its safety. Therefore, guidelines are against the routine use of manual TA during primary PCI. Our study aimed to evaluate the immediate angiographic results of the TA to assess the predictive factors of its failure. An observational prospective study was performed from 2016 to 2018. We included all patients who underwent TA using the ExportTM catheter during a primary PCI for less than 12 h of STEMI. The primary endpoint was the failure of TA assessed by TIMI classification for the final coronary flow. Insufficient reperfusion due to failed TA was defined as a TIMI flow < 3 in the culprit artery at the end of the PCI. The secondary composite endpoint was the occurrence of in-hospital Major Adverse CerebroCardiovascular Events (MACCE). We have included 60 consecutive patients. Mean age was 59.7 ± 13.6 years. 81.7% were males. Anterior location of STEMI was noted in 60%. The median delay between symptoms and wire crossing was 5 [3.8-8.7] hours. Initially, 68.3% of the patients presented a TIMI 0 flow and final TIMI 3 flow was established in 66.7% of cases. We identified 4 patients with in-hospital MACCE. Our results suggest a high rate of angiographic failure(33.3%) following a primary PCI despite the use of TA. The associate factors of a failure TA were: the delay between symptoms onset and wire crossing ≥ 5h( P = 0.025) and a cardiogenic shock( P = 0.04). The multivariate study showed that tardive presentation (> 5 h) was the only predictive factor of a failed TA HR = 4 [1.1-14], P = 0.037. Despite the limitation of our observational study, we noted an important rate of slow and no flow in the setting of primary PCI despite using TA. Identifying such risk factors will improve the effectiveness of the primary PCI with a selective TA.

724 Cardiovascular morbidity and mortality related to non-alcoholic fatty liver disease: a systematic review and meta-analysis of prospective studies

Abstract Aims Whether non-alcoholic fatty liver disease (NAFLD) is a risk factor for cardiovascular (CV) events is still debated. Currently available evidence derives from non-homogeneous studies yielding conflicting results. We set out to assess the relationship between NAFLD and CV morbidity and mortality by pooling results of previous studies. Methods We performed a systematic review and meta-analysis of prospective observational studies published from 1966 through 2021 reporting summary-level outcome data in subjects with and without NAFLD. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality, CV mortality, myocardial infarction (MI), stroke, major adverse cerebrocardiovascular events (MACCE) and atrial fibrillation (AF) were pooled through inverse variance random-effect meta-analysis to compute the summary effect size. We performed post hoc subgroup analysis stratified by geographical region and univariate mixed-effect model meta-regression analysis to address statistical heterogeneity. Results We identified a total of 29 studies pooling an overall population of 5 626 573 middle-aged individuals (mean age 56 ± 8; male sex 53%; NAFLD 5.8%, n = 326 389). Mean follow-up was 10 ± 6 years. Compared with control population, presence of NAFLD was associated with similar risk of all-cause death (RR 1.17; 95% CI 0.89–1.52) and CV death (RR 0.84; 95% CI 0.64–1.10). When analysed by geographic location, pooled estimates of RR (95% CI) for all-cause death were 1.57 (1.00–2.48) for Western countries, and 0.81 (0.52–1.1.26) for Eastern countries (test for subgroup difference, P = 0.04). Meta-regression analysis showed a stronger relationship between NAFLD and all-cause mortality proportional to increasing body mass index (P = 0.048). NAFLD was associated with increased risk of myocardial infarction (RR 1.35; 95% CI 1.09–1.68), stroke (RR 1.20; 95% CI 1.06–1.35), MACCE (RR 2.09; 95% CI 1.57–2.78), and atrial fibrillation (RR 1.37; 95% CI 1.05–1.78). Conclusion NAFLD portends excess all-cause mortality but only in Western countries. CV mortality was similar in NAFLD and non-NAFLD groups. NAFLD is associated with increased risk of incident MI, stroke, MACCE, and AF.