Risk Of Adverse Cardiovascular Outcomes Research Articles

Early Rhythm Control Therapy for Atrial Fibrillation in Low-Risk Patients : A Nationwide Propensity Score-Weighted Study.

Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA2DS2-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial). To investigate whether the results can be generalized to patients with low stroke risk. Population-based cohort study. Nationwide claims database of the Korean National Health Insurance Service. 54216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis. The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA2DS2-VASc score, approximately 0 to 1) using propensity overlap weighting. In total, 37557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA2DS2-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA2DS2-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility. Residual confounding. In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility. The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea.

Identifying a metabolomics profile associated with masked hypertension in two independent cohorts: Data from the African-PREDICT and SABPA studies.

Individuals with masked hypertension (MHT) have a greater risk of adverse cardiovascular outcomes than normotensive (NT) individuals. Exploring metabolomic differences between NT and MHT individuals may help provide a better understanding of the etiology of MHT. We analyzed data from 910 young participants (83% NT and 17% MHT) (mean age 24 ± 3 years) from the African-PREDICT and 210 older participants (63% NT and 37% MHT) from the SABPA (mean age 42 ± 9.6 years) studies. Clinic and ambulatory blood pressures (BPs) were used to define BP phenotypes. Urinary amino acids and acylcarnitines were measured using liquid chromatography time-of-flight mass spectrometry in SABPA and liquid chromatography tandem mass spectrometry in the African-PREDICT studies. In the SABPA study, amino acids (leucine/isoleucine, valine, methionine, phenylalanine), free carnitine (C0-carnitine), and acylcarnitines C3 (propionyl)-, C4 (butyryl)-carnitine and total acylcarnitine) were higher in MHT than NT adults. In the African-PREDICT study, C0- and C5-carnitines were higher in MHT individuals. With unadjusted analyses in NT adults from the SABPA study, ambulatory SBP correlated positively with only C3-carnitine. In MHT individuals, positive correlations of ambulatory SBP with leucine/isoleucine, valine, methionine, phenylalanine, C0-carnitine and C3-carnitine were evident (all p < 0.05). In the African-PREDICT study, ambulatory SBP correlated positively with C0-carnitine (r = 0.101; p = 0.006) and C5-carnitine (r = 0.195; p < 0.001) in NT adults and C5-carnitine in MHT individuals (r = 0.169; p = 0.034). We demonstrated differences between the metabolomic profiles of NT and MHT adults, which may reflect different stages in the alteration of branched-chain amino acid metabolism early on and later in life.

Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts

BackgroundHigh glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control.ObjectivesWe investigated the possible effects of GlycACE2 on the anti-remodeling pathways of the RAS inhibitors by evaluating the levels of Angiotensin (Ang) 1–9, Ang 1–7, and Mas receptor (MasR), Nuclear-factor of activated T-cells (NFAT), and fibrosis in human hearts.MethodsWe evaluated 197 first HTX recipients (107 non-T2DM, 90 T2DM). All patients were treated with angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) at hospital discharge. Patients underwent clinical evaluation (metabolic status, echocardiography, coronary CT-angiography, and endomyocardial biopsies). Biopsies were used to evaluate ACE2, GlycACE2, Ang 1–9, Ang 1–7, MasR, NAFT, and fibrosis.ResultsGlycACE2 was higher in T2DM compared tonon-T2DM cardiomyocytes. Moreover, reduced expressions of Ang 1–9, Ang 1–7, and MasR were observed, suggesting impaired effects of RAS-inhibition in diabetic hearts. Accordingly, biopsies from T2DM recipients showed higher fibrosis than those from non-T2DM recipients. Notably, the expression of GlycACE2 in heart biopsies was strongly dependent on glycemic control, as reflected by the correlation between mean plasma HbA1c, evaluated quarterly during the 12-month follow-up, and GlycACE2 expression.ConclusionPoor glycemic control, favoring GlycACE2, may attenuate the cardioprotective effects of RAS-inhibition. However, the achievement of tight glycemic control normalizes the anti-remodeling effects of RAS-inhibition.Trial registration: https://clinicaltrials.gov/ NCT03546062.

Long-term risk of adverse cardiovascular outcomes associated with cutaneous lupus erythematosus: a nationwide cohort study.

Autoimmune diseases, including systemic lupus erythematosus, have been associated with a substantial risk of cardiovascular morbidity and mortality. However, data on the long-term risk of incident heart failure and other adverse cardiovascular outcomes among patients diagnosed with cutaneous lupus erythematosus (CLE) are limited. In this cohort study, all patients ≥ 18years with newly diagnosed CLE between 1996 and 2018 were identified through Danish nationwide registries and matched 1:4 by age, sex, and comorbidity with individuals without CLE. Incident adverse cardiovascular outcomes, including heart failure, were compared between the matched groups, overall, and according to sex. Of 2085 patients diagnosed with CLE, 2062 patients were matched with 8248 control subjects from the Danish background population (median age 50years [25th-75th percentile: 37-62years]; 22.3% men). The median follow-up was 6.2years. The 10-year cumulative incidences and adjusted hazard ratios (HR) of outcomes were as follows: heart failure: 3.29% (95% CI, 2.42-4.36%) for CLE patients versus 2.59% (2.20-3.02%) for the background population, HR 1.67 (95% CI, 1.24-2.24); atrial fibrillation or flutter: 5.15% (3.99-6.52%) versus 3.84% (3.37-4.36%), HR 1.40 (1.09-1.80); the composite of ICD implantation, ventricular arrhythmia, or cardiac arrest: 0.72% (0.34-1.40%) versus 0.44% (0.29-0.64%), HR 1.71 (0.85-3.45); the composite of pacemaker implantation, atrioventricular block, or sinoatrial dysfunction: 0.91% (0.48-1.59%) versus 0.54% (0.37-0.76%), HR 1.32 (0.72-2.41); myocardial infarction: 3.05% (2.18-4.15%) versus 1.59% (1.29-1.93%), HR 2.15 (1.53-3.00); ischemic stroke: 3.25% (2.38-4.32%) versus 2.50% (2.13-2.93%), HR 1.56 (1.16-2.10); and venous thromboembolism: 2.74% (1.94-3.75%) versus 2.05% (1.71-2.44%), HR 1.60 (1.16-2.21). Sex did not modify the association between CLE and adverse cardiovascular outcomes (Pinteraction ≥ 0.12 for all outcomes). Patients with CLE had a higher associated risk of adverse cardiovascular outcomes compared with the background population, irrespective of sex. Key Points • Findings: In this nationwide cohort study, including 2062 patients with cutaneous lupus erythematosus and 8248 matched controls, cutaneous lupus erythematosus was associated with an increased long-term risk of heart failure, cardiac arrhythmias, and thromboembolic events, irrespective of sex.

Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk: Findings From Population-Based Cohort Studies

BackgroundSupranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic implication of supranormal left ventricular ejection fraction (LVEF)—assessed by cardiac magnetic resonance (CMR)—in healthy, community-dwelling individuals is unknown. ObjectivesThe purpose of this study is to investigate the prognostic implication of supranormal LVEF as assessed by CMR and its inter-relationship with stroke volume among community-dwelling adults without CVD. MethodsParticipants from the MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) cohorts free of CVD who underwent CMR with LVEF above the normal CMR cutoff (≥57%) were included. The association between cohort-specific LVEF categories and risk of clinically adjudicated major adverse cardiovascular events (MACE) was assessed using adjusted Cox models. Subgroup analysis was also performed to evaluate the association of LVEF and risk of MACE among individuals stratified by left ventricular stroke volume index. ResultsThe study included 4,703 participants from MESA and 2,287 from DHS with 727 and 151 MACE events, respectively. In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs Q1) in both cohorts after accounting for potential confounders (MESA: HR = 1.27 [95% CI: 1.01-1.60], P = 0.04; DHS: HR = 1.72 [95% CI: 1.05-2.79], P = 0.03). A significant interaction was found between the continuous measures of LVEF and left ventricular stroke volume index (P interaction = 0.02) such that higher LVEF was significantly associated with an increased risk of MACE among individuals with low but not high stroke volume. ConclusionsAmong community-dwelling adults without CVD, LVEF in the supranormal range is associated with a higher risk of adverse cardiovascular outcomes, particularly in those with lower stroke volume.

Antihypertensive and Statin Medication Adherence Among Medicare Beneficiaries

Medication adherence is important for optimal management of chronic conditions, including hypertension and hypercholesterolemia. This study describes adherence to antihypertensive and statin medications, individually and collectively, and examines variation in adherence by demographic and geographic characteristics. The 2017 prescription drug event data for beneficiaries with Medicare Part D coverage were assessed. Beneficiaries with a proportion of days covered ≥80% were considered adherent. Adjusted prevalence ratios were estimated to quantify the associations between demographic and geographic characteristics and adherence. Adherence estimates were mapped by county of residence using a spatial empirical Bayesian smoothing technique to enhance stability. Analyses were conducted in 2019‒2021. Among the 22.5 million beneficiaries prescribed antihypertensive medications, 77.1% were adherent; among the 16.1 million prescribed statin medications, 81.9% were adherent; and among the 13.5 million prescribed antihypertensive and statin medications, 70.3% were adherent to both. Adherence varied by race/ethnicity: American Indian/Alaska Native (adjusted prevalence ratio=0.83, 95% confidence limit=0.82, 0.842), Hispanic (adjusted prevalence ratio=0.90, 95% confidence limit=0.90, 0.91), and non-Hispanic Black (adjusted prevalence ratio=0.87, 95% confidence limit=0.86, 0.87) beneficiaries were less likely to be adherent than non-Hispanic White beneficiaries. County-level adherence ranged across the U.S. from 25.7% to 88.5% for antihypertensive medications, from 36.0% to 93.8% for statin medications, and from 20.8% to 92.9% for both medications combined and tended to be the lowest in the southern U.S. This study highlights opportunities for efforts to remove barriers and support medication adherence, especially among racial/ethnic minority groups and within the regions at greatest risk for adverse cardiovascular outcomes.

Cardiac cycle: an observational/interventional study protocol to characterise cardiopulmonary function and evaluate a home-based cycling program in children and adolescents born extremely preterm

IntroductionExtremely preterm (EP)/extremely low birthweight (ELBW) individuals may have an increased risk for adverse cardiovascular outcomes. Compared with term-born controls, these individuals have poorer lung function and reduced exercise capacity....

Reduced Physical Activity During COVID-19 in Children With Congenital Heart Disease: A Longitudinal Analysis

BackgroundCoronavirus disease 2019 (COVID-19) was associated with a reduction in physical activity in children with congenital heart disease (CHD) in early 2020. Given the increased cardiovascular risk of this population, optimizing cardiovascular health behaviour is important. The aim of the study is to determine how the ongoing COVID-19 pandemic has impacted longitudinal physical activity measures in children with CHD.MethodsAs part of a prospective cohort study, children and adolescents aged 9-16 years old with moderate-to-complex CHD were recruited from British Columbia Children’s Hospital and partnership clinics across British Columbia and the Yukon territory. Daily step counts were measured continuously over 3 years (2018-2021) with Fitbit Charge 2. School status during the COVID-19 pandemic was assessed with parent- or self-report survey.ResultsA total of 102, 114, and 93 participants had valid Fitbit data during 2018, 2019, and 2020, respectively. There was a significant reduction in the annual mean step count for 2020 (8225 ± 4328 steps) compared with both 2018 (9416 ± 3770 steps) and 2019 (9533 ± 4114 steps) (P < 0.001). There was a loss of seasonal variation in physical activity, and reduced levels of physical activity persisted when most children resumed in-person schooling in September 2020.ConclusionsWe demonstrated a significant decrease in physical activity and loss of seasonal patterns in children with CHD during 2020. These findings represent a worsening of the cardiovascular risk profile in children with CHD, who are already at an increased risk of adverse cardiovascular outcomes. Mitigation strategies are needed to optimize the cardiovascular health status of children with CHD as the pandemic persists.

NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient

Although statins are generally well tolerated, statin intolerance is reported in 5-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes. This Scientific Statement from the National Lipid Association was developed to provide an updated definition of statin intolerance and to inform clinicians and researchers about its identification and management. Statin intolerance is defined as one or more adverse effects associated with statin therapy which resolves or improves with dose reduction or discontinuation and can be classified as a complete inability to tolerate any dose of a statin or partial intolerance with inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. To classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest approved daily dosage. This Statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect (patient expectation of harm resulting in perceived side effects). To identify a tolerable statin regimen it is recommended that clinicians consider using several different strategies (e.g., different statin, dose, and/or dosing frequency). Non-statin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy. If so, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored. In high and very high risk patients who are statin intolerant, clinicians should consider initiating non-statin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins.

IDENTIFYING A METABOLOMICS PROFILE ASSOCIATED WITH MASKED HYPERTENSION IN TWO INDEPENDENT COHORTS: DATA FROM THE AFRICAN-PREDICT AND SABPA STUDIES

Objective: Individuals with masked hypertension (MHT) have a greater risk of adverse cardiovascular outcomes compared to normotensives (NT). Exploring metabolomic differences between NT and MHT individuals may help provide a better understanding of the aetiology of MHT. Design and method: We analysed the data of N = 910 young apparently healthy participants (83% NT and 17% MHT) (mean age 24 ± 3 years) from the African-PREDICT and N = 210 older participants (63% NT and 37% MHT) from the SABPA (mean age 42 ± 9.6 years) studies. Clinic and ambulatory blood pressures (BPs) were used to define BP phenotypes. Urinary amino acids and acylcarnitines were measured using liquid chromatography time-of-flight mass spectrometry in the SABPA and liquid chromatography tandem mass spectrometry in the African-PREDICT studies. Results: Clinic and 24hr BPs were higher in MHT compared to NT adults (all p &lt; 0.001). In the SABPA study, amino acids (leucine/isoleucine, valine, methionine and phenylalanine) and acylcarnitines (C0-, C3-, C4- and total acylcarnitines) were more abundant in MHT than NT adults. In the African-PREDICT study, only C0- and C5-carnitines were higher in MHT. When adjusting for waist circumference, all differences between NT and MHT individuals became non-significant for both studies (all q&gt; 0.05). With unadjusted analyses in NT adults from the SABPA study, 24hr SBP correlated positively with only C3-carnitine. Conversely in MHT, positive correlations of 24hr SBP with leucine/isoleucine, valine, methionine, phenylalanine, C0- and C3-carnitine were evident (all p &lt; 0.05). In the African-PREDICT study, 24hr SBP correlated positively with C0- (r = 0.101; p = 0.006) and C5-carnitine (r = 0.195; p &lt; 0.001) in NT adults, and C5-carrnitine in MHT (r = 0.169; p = 0.034). Conclusions: Using two independent cohorts, we demonstrated significant differences between the metabolomic profiles of NT and MHT adults, which may reflect different stages in the alteration of branched-chain amino acid (BCAA) metabolism early on and later in life. These changes in BCAA metabolism are also likely modulated by central adiposity.

Surgery for Epiglottic Collapse in OSA Patients

Obstructive sleep apnea (OSA) is a common clinical entity, impacting millions of people worldwide. This condition stems from abnormal anatomical and physiological features, leading to intermittent upper airway collapse during sleeping hours. It has been well established that patients suffering from OSA are at increased risk for adverse cardiovascular outcomes if not properly diagnosed and treated in time. Aside from non-invasive treatments, such as positive airway pressure (PAP) masks, several surgical modalities have been shown to successfully reduce the severity and frequency of upper airway collapse. However, because different pathological mechanisms play a role in the pathophysiology of each patient’s condition, a more individualized approach is needed. One such mechanism is epiglottic collapse, which has been yet to be adequately studied and understood. Furthermore, the volume of medical literature addressing the role of epiglottic collapse in OSA and its association with different treatment outcomes is scarce. In this review of the literature, our aim was to present the current existing knowledge regarding epiglottic collapse, its role in the pathophysiology of OSA and the management of OSA associated with epiglottic collapse. We conclude that further research is needed in order to formulate quality evidence-based clinical guidelines regarding the issue at hand.

Age and Outcomes of Early Rhythm Control in Patients With Atrial Fibrillation

This study sought to investigate whether the effects of early rhythm control differ according to age. Rhythm control, compared with usual care among patients recently diagnosed with atrial fibrillation (AF), was found to be associated with a lower risk of adverse cardiovascular outcomes. It is unclear whether the results can be generalized for older adults. This retrospective population-based cohort study included 31,220 patients with AF, from the Korean National Health Insurance Service database, undergoing rhythm control (antiarrhythmic drugs or ablation) or rate control therapy, initiated within 1 year of AF diagnosis. A composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared in subgroups stratified by age. Compared with rate control, early rhythm control was associated with a lower risk of the primary composite outcome in patients<75 years of age (HR: 0.80; 95%CI: 0.72-0.88). The protective association between early rhythm control and cardiovascular outcomes exhibited a linear decrease with advancing age, with declined benefits in patients≥75 years of age (HR: 0.94; 95%CI: 0.87-1.03; Pinteraction=0.045). Trends toward lower risks of ischemic stroke (HR: 0.78; 95%CI: 0.67-0.90) and acute myocardial infarction (HR: 0.63; 95%CI: 0.41-0.97) were observed in the older adults. No significant differences in safety outcomes were found across different ages. The beneficial association of early rhythm control with cardiovascular outcomes was attenuated with increasing age, with the larger benefits in younger patients<75 years of age. No differences were found by age in treatment-related safety outcomes.

Prognostic Role of Residual Thrombus Burden Following Thrombectomy: Insights From the TOTAL Trial.

It is unclear whether more effective forms of thrombus removal than current aspiration catheters would lead to improved outcomes. We sought to evaluate the prognostic role of residual thrombus burden (rTB), after manual thrombectomy, in patients undergoing primary percutaneous coronary intervention with routine manual thrombectomy in the TOTAL trial (Thrombectomy Versus PCI Alone). This is a single-arm analysis of patients from the TOTAL trial who underwent routine manual aspiration thrombectomy. The rTB was quantified by an angiographic core laboratory using the Thrombolysis in Myocardial Infarction criteria and validated using existing optical coherent tomography data. Large rTB was defined as grade ≥3. The primary outcome was death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or new or worsening heart failure within 180 days. Of 5033 patients randomized to routine thrombectomy, 2869 patients had quantifiable rTB (1014 [35%] had large rTB). Patients with large rTB were more likely to have hypertension, previous percutaneous coronary intervention, myocardial infarction, or Killip class III on presentation but less likely to have Killip class I. The primary outcome occurred more frequently in patients with large rTB, even after adjustment for known risk predictors (8.6% versus 4.6%; adjusted hazard ratio, 1.83 [95% CI, 1.34-2.48]). These patients also had a higher risk of cardiovascular death (adjusted hazard ratio, 1.83 [95% CI, 1.13-2.95]), cardiogenic shock (adjusted hazard ratio, 2.02 [95% CI, 1.08-3.76]), and heart failure (adjusted hazard ratio, 1.74 [95% CI, 1.02-2.96]) but not myocardial infarction or stroke. Large rTB is a common finding in primary percutaneous coronary intervention and is associated with increased risk of adverse cardiovascular outcomes, including cardiovascular death. Future technologies offering better thrombus removal than current devices may decrease or even eliminate the risk associated with rTB. This, potentially, can turn into a strategic option to be studied in clinical trials. URL: https://www. gov; Unique identifier: NCT01149044.

Association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Use With Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus Patients With Stabilized Acute Myocardial Infarction: A Propensity Score Matching Study.

BackgroundCoronary artery disease (CAD) is one of the leading causes of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM), who are at a greater risk of acute myocardial infarction (AMI) and sudden cardiac death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce cardiovascular events and mortality in T2DM patients with a risk of cardiovascular disease. This study aimed to investigate the effect of SGLT2 inhibitor use on the adverse cardiovascular and renal outcomes in T2DM patients with AMI.MethodsA total of 1,268 patients admitted to the Coronary Care Unit due to AMI were retrospectively screened.Patients taking SGLT2 inhibitors before or during the index AMI hospitalization were assigned as group 1. Patients who never received SGLT2 inhibitors were assigned as group 2. Patients in groups 1 and 2 were matched in a 1:2 ratio, and 198 T2DM patients with stabilized AMI were retrospectively enrolled for the final analysis.ResultsWith a mean follow-up period of 23.5 ± 15.7 months, 3 (4.5%) patients in group 1 and 22 (16.7%) patients in group 2 experienced rehospitalization for acute coronary syndrome (ACS), while 1 (1.5%) patient in group 1 and 7 (5.3%) patients in group 2 suffered sudden cardiac death. The Kaplan–Meier curves demonstrated that the patients in group 1 had a lower risk of adverse cardiovascular outcomes. According to the multivariate analysis, the baseline estimated glomerular filtration rate (eGFR) (P = 0.008, 95% CI: 0.944–0.991) and the use of SGLT2 inhibitors (P = 0.039, 95% CI: 0.116–0.947) were both independent predictors of adverse cardiovascular outcomes. On the other hand, the use of SGLT2 inhibitors was not associated with adverse renal outcomes.ConclusionIn T2DM patients with stabilized AMI, the use of SGLT2 inhibitors was associated with a lower risk of adverse cardiovascular outcomes. In addition, the baseline renal function was also an independent predictor of adverse cardiovascular outcomes.

Thoracic Aortic Diameter and Cardiovascular Events and Mortality among Women and Men.

Background Thoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events. Purpose To evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality. Materials and Methods Study participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters. Results A total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes. Conclusion Larger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men. Clinical trial registration no. NTR6831 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Williams in this issue.

Change in Left Ventricular Ejection Fraction With Coronary Artery Revascularization and Subsequent Risk for Adverse Cardiovascular Outcomes.

Coronary revascularization is recommended to treat ischemic cardiomyopathy. However, the relations of revascularization-associated ejection fraction (EF) change to subsequent outcomes have not been elucidated. In 10 071 veterans (mean age 67 years; 1% women; 15% non-White) who underwent a first percutaneous coronary intervention (PCI) or coronary artery bypass grafting between January 1, 1995, and December 31, 2010, and had prerevascularization and postrevascularization EF measured, we calculated delta-EF (postprocedure EF-preprocedure EF). We related delta-EF as a continuous measure and as categories (≤-5, -5<delta-EF<0, delta-EF=0, 0<delta-EF<5, and delta-EF≥5) to death (using Cox regression) and heart failure hospitalization days (using negative binomial regression) in multivariable-adjusted models, for total sample, and PCI and coronary artery bypass grafting strata. Over follow-up (mean/maximum 5/14 years) 56% died. Each 5% improvement in delta-EF was associated with statistically significant reductions in death and heart failure hospitalization days of 5% (95% CI, 3%-7%) and 10% (95% CI, 5%-15%), respectively, in the total sample and 6% (95% CI, 4%-8%) and 10% (95% CI, 5%-16%), respectively, in the PCI subgroup. Patients in the highest delta-EF category had 27% (95% CI, 19%-34%) lower mortality (30% [95% CI, 21%-37%] lower in PCI stratum) and ≈40% lower heart failure hospitalization days in total sample and PCI stratum, compared with those in the lowest category. Relations of delta-EF and outcomes in coronary artery bypass grafting subgroup did not reach statistical significance. Revascularization-associated EF improvement was associated with significant reductions in mortality and heart failure hospitalization burden, particularly in the PCI subgroup.

Step-by-step diagnosis and management of the nocebo/drucebo effect in statin-associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP).

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin‐associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3–5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)—what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real‐world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step‐by‐step patient‐centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long‐term compliance with lipid‐lowering therapy.

Exercise Blood Pressure in Heart Failure With Preserved and Reduced Ejection Fraction

ObjectivesThis study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF). BackgroundIn HFpEF, determinants and consequences of exercise BP pulsatility are not well understood. MethodsWe measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population. ResultsIn HFpEF, only age (standardized beta = 0.593; P < 0.001), exercise stroke volume (standardized beta = 0.349; P < 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004). ConclusionsIn HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome.

Visit-to-Visit Heart Rate Variability Is Positively Associated With the Risk of Adverse Cardiovascular Outcomes.

IntroductionPrevious studies found visit-to-visit heart rate variability (VVHRV) may be positively associated with risks of several cardiovascular events, but whether VVHRV affected the benefit of intensive blood pressure control remained unknown. In this study, we assessed the risk of the composite cardiovascular outcomes associated with VVHRV among the older patients with hypertension and evaluated whether the benefit of intensive blood pressure control in the prevention of the composite cardiovascular outcomes was consistent in the context of elevated VVHRV.MethodsThis was a post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). We explored the relationship between VVHRV and the composite cardiovascular outcomes by multivariate Cox proportional hazard regressions. The primary endpoint was the composite cardiovascular outcomes, same as SPRINT, defined as a composite of myocardial infarction, stroke, heart failure, and/or death from cardiovascular causes. We used multiple adjustment models for all regressions.ResultsNine thousand two hundred and fourty-seven patients from the SPRINT were included in our analysis. We found a positive association between VVHRV and the risk of composite cardiovascular outcomes among the elderly with hypertension. Per 1 CV increment in HRCV, the hazard ratio of the risk of composite cardiovascular outcomes was 1.04 (95CI: 1.03, 1.05) in the fully adjusted Model. The benefit of intensive blood pressure control in managing cardiovascular events was consistent in different VVHRV subgroups. There was no significant interaction in other confounders.ConclusionWe found the VVHRV was associated with the composite cardiovascular outcomes among the elderly with hypertension, intensive blood pressure control did not change the above association, and the benefits of intensive blood pressure management were consistent across different VVHRV groups.

Abstract P184: Racial Differences In Mental Stress-induced Transient Endothelial Dysfunction And Its Association With Cardiovascular Outcomes

Background: An established link exists between acute mental stress and the development of transient endothelial dysfunction (TED) as assessed by brachial artery flow-mediated vasodilation (FMD). Black individuals have a high burden of cardiovascular (CV) risk factors and social disadvantages, which may result in adverse vascular responses to stress. We investigated differences in TED with mental stress in Black and non-Black individuals with coronary artery disease (CAD), and whether TED is associated with CV outcomes in both groups. Methods: We enrolled 812 patients with stable CAD between June 2011 and March 2016 and followed them through February 2020. Study participants were subjected to a public-speaking mental stress task and FMD (derived from % vasodilation with brachial artery hyperemia testing) was assessed by ultrasound before and 30 minutes after mental stress. TED was defined as a lower post-stress FMD than pre-stress FMD. We compared pre-stress FMD, post-stress FMD, and TED between Black and non-Black participants. In both groups, we examined the association of TED with an adjudicated composite end point of CV death and myocardial infarction (MI) after adjusting for demographic, clinical, and socioeconomic factors. Both first and recurring events were counted and multivariable models for repeated events were used for analysis. Results: The mean (SD) age was 59 (10) years, and 328 (40%) were Black. Pre-stress FMD was lower in Black than non-Black participants [3.7 (2.8) vs. 4.9 (3.8) p&lt;0.001], and significantly declined with mental stress in both groups. TED occurred more often in Black (76%) than non-Black patients (67%), age- and sex-adjusted OR, 1.6, 95% CI, 1.4-1.7). Race related differences in TED persisted after adjustment for demographic factors, CAD risk factors and medications (Black vs. non-Black OR, 1.6, 95% CI, 1.5-1.7). After further adjusting for socioeconomic indicators (education, income, and employment status), TED remained elevated in Black patients (OR, 1.4 (95% CI, 1.3-1.6). Over a median (interquartile range) follow-up period of 75 (65-82) months, 142 (18%) patients had at least one event. Development of TED with mental stress was associated with an increased risk for the study outcome both in Black (age- and sex-adjusted HR, 3.0; 95% CI, 1.3-6.8) and non-Black participants (HR, 1.7, 95% CI, 0.96-3.0), p=0.26 for interaction. Adjustment for demographic, clinical and socioeconomic factors did not diminish these associations. Conclusions: Among CAD patients, Black individuals are more likely than non-Black individuals to develop endothelial dysfunction with mental stress, which in turn is associated with an increased risk of adverse cardiovascular events. Endothelial dysfunction in response to psychological stress may represent an important mechanism for the disproportionate risk of adverse CV outcomes in Black patients.