Statin use and the risk of CVD events,stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis

AimsConsidering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention.Data synthesisThe MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69–0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65–0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70–0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63–0.85, P < 0.0001).ConclusionsStatin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes.Systematic review registrationPROSPERO CRD42021281132.     

The relationship of skin autofluorescence with diastolic function and HFA-PEFF score in a general population of older people

Background and aimsAdvanced glycation end-products accumulation in tissue as measured by Skin autofluorescence (SAF) is related to diastolic function in specific patient populations. This analysis aims at investigating this relationship in a general population of older persons.Methods and resultsBased on data from the CARLA cohort at first follow-up, 245 subjects were analyzed and stratified according to cardiovascular risk factors (CVRF). We used linear regression to investigate the association between diastolic function evaluated by echocardiography, HFA-PEFF score, and SAF.Univariable regression analysis showed an association of SAF with septal-E/e’ (standardised beta = 1.11, 95% CI = 0.51–1.71) and A (3.42, 95% CI = 0.72–6.12), the former persisting after adjustment for age, sex and CVRF (0.67, 95% CI = 0.05–1.28). Septal-E/e’ remained related to SAF only in the high cardiovascular risk stratum (1.16, 95% CI = 0.26–2.06). SAF was related to HFA-PEFF score (0.27, 95% CI = 0.10–0.43) but not after correcting for age and sex (0.16, 95% CI = 0.00–0.32) and CVRF and glomerular filtration rate (0.12, 95% CI = ?0.07 – 0.27). SAF was related to the HFA-PEFF score only for participants with high cardiovascular risk (0.23, 95% CI = 0.02–0.45).ConclusionIn a general community-dwelling older population, SAF is related to diastolic function as measured by septal-E/e’. Further research is necessary to assess if SAF is a potential screening tool for diastolic dysfunction in advanced age.     

Impact of serum phosphate on severity and functional outcomes after ischemic stroke in young adults

Background and aimsSerum phosphate is an essential nutrient that plays multiple physiological roles in cardiovascular function. The aim of this study was to investigate the association between serum phosphate and stroke severity and prognosis in ischemic stroke and transient ischemic attack (TIA) among young adults.Methods and resultsWe retrospectively recruited patients with acute ischemic stroke and TIA aged 18–45 years. The primary outcome was 90-day poor functional outcome (modified Rankin Scale score of 2–6). The secondary outcomes included stroke severity (NIHSS ≥5 was defined as moderate to severe stroke) and poor functional outcome at hospital discharge. A total of 687 patients with a mean age of 36.8 years were enrolled. Lower serum phosphate levels were significantly associated with more severe stoke (P for trend = 0.017). Compared with the fourth quartile, the odds ratio (95% CI) of the first quartile was 1.85 (1.19–3.22) for moderate to severe stroke. After adjusting for confounders other than stroke severity, the odds ratio (95% CI) of the first quartile was 1.74 (1.06–2.86) for poor functional outcome at hospital discharge and 1.90 (1.09–3.31) at 90-day follow-up compared with the fourth quartile. However, the significant association between serum phosphate and poor functional outcomes disappeared after stroke severity was further adjusted.ConclusionsSerum phosphate is more likely a marker of stroke severity than a contributor to poor functional outcomes after ischemic stroke and TIA in young adults. Lower serum phosphate levels were associated with more severe stroke.     

Smoking and alcohol consumption influence the risk of cardiovascular diseases in Korean adults with elevated blood pressure

Background and aimsCardiovascular disease (CVD) and hypertension are the main causes of global death. We aimed to investigate the independent and combined effects of smoking and alcohol consumption on CVD risk among Koreans with elevated blood pressure (BP).Methods and resultsAdults aged 20–65 years with elevated BP and without pre-existing CVDs were selected from the National Health Insurance Service-National Sample Cohort version 2.0. We followed up 59,391 men and 35,253 women between 2009 and 2015. The association of CVD incidence with smoking pack-years and alcohol consumption was investigated using the multivariate Cox proportional hazard model. Among women, smokers (10.1–20.0 pack-years) and alcohol drinkers (≥30.0 g/day) had higher CVD risks (hazard ratio [HR] = 1.15, 95% confidence intervals [CI] 1.06–1.25, HR = 1.06, 95% CI 1.00–1.12, respectively) compared to each referent group. However, men who smoked exhibited an increased CVD risk only with pack-years >20.0 (HR = 1.09, 1.03–1.14 and HR = 1.18, 1.11–1.26 for smokers with 20.1–30.0 and ≥ 30.1 pack-years, respectively) compared to nonsmokers. In the combined groups of those smoking and consuming alcohol, only nonsmoking men consuming alcohol 1.0–29.9 g/day had a lower CVD risk than did nonsmoking, nondrinking men (HR = 0.90, 0.83–0.97). Women smoking 1.0-10.0 pack-years and consuming alcohol ≥30.0 g/day had a higher CVD risk (HR = 1.25, 1.11–1.41) than nonsmoking and nondrinking women.ConclusionSmoking and alcohol consumption, independently and jointly, were associated with CVD risk in men and women. Women had a greater CVD risk than did men among Korean adults with elevated BP.     

Aspirin for Primary Prevention of Cardiovascular Events

BackgroundThe efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) remain debatable.ObjectivesThe purpose of this study was to examine the clinical outcomes with aspirin for primary prevention of CVD after the recent publication of large trials adding >45,000 individuals to the published data.MethodsRandomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events. Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.ResultsA total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Compared with control, aspirin was associated with similar all-cause death (RR: 0.97; 95% confidence interval [CI]: 0.93 to 1.01), CV death (RR: 0.93; 95% CI: 0.86 to 1.00), and non-CV death (RR: 0.98; 95% CI: 0.92 to 1.05), but a lower risk of nonfatal MI (RR: 0.82; 95% CI: 0.72 to 0.94), TIA (RR: 0.79; 95% CI: 0.71 to 0.89), and ischemic stroke (RR: 0.87; 95% CI: 0.79 to 0.95). Aspirin was associated with a higher risk of major bleeding (RR: 1.5; 95% CI: 1.33 to 1.69), intracranial bleeding (RR: 1.32; 95% CI: 1.12 to 1.55), and major GI bleeding (RR: 1.52; 95% CI: 1.34 to 1.73), with similar rates of fatal bleeding (RR: 1.09; 95% CI: 0.78 to 1.55) compared with the control subjects. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.ConclusionsAspirin for primary prevention reduces nonfatal ischemic events but significantly increases nonfatal bleeding events.     

Contribution of metabolic risk factors and lifestyle behaviors to cardiovascular disease: A mendelian randomization study

Background and aimsEtiologic associations between some modifiable factors (metabolic risk factors and lifestyle behaviors) and cardiovascular disease (CVD) remain unclear. To identify targets for CVD prevention, we evaluated the causal associations of these factors with coronary artery disease (CAD) and ischemic stroke using a two-sample Mendelian randomization (MR) method.Methods and resultsPreviously published genome-wide association studies (GWASs) for blood pressure (BP), glucose, lipids, overweight, smoking, alcohol intake, sedentariness, and education were used to identify instruments for 15 modifiable factors. We extracted effects of the genetic variants used as instruments for the exposures on coronary artery disease (CAD) and ischemic stroke from large GWASs (N = 60 801 cases/123 504 controls for CAD and N = 40 585 cases/406 111 controls for ischemic stroke). Genetically predicted hypertension (CAD: OR, 5.19 [95% CI, 4.21–6.41]; ischemic stroke: OR, 4.92 [4.12–5.86]), systolic BP (CAD: OR, 1.03 [1.03–1.04]; ischemic stroke: OR, 1.03 [1.03–1.03]), diastolic BP (CAD: OR, 1.05 [1.05–1.06]; ischemic stroke: OR, 1.05 [1.04–1.05]), type 2 diabetes (CAD: OR, 1.11 [1.08–1.15]; ischemic stroke: OR, 1.07 [1.04-1.10]), smoking initiation (CAD: OR, 1.26 [1.18–1.35]; ischemic stroke: OR, 1.24 [1.16–1.33]), educational attainment (CAD: OR, 0.62 [0.58–0.66]; ischemic stroke: OR, 0.68 [0.63–0.72]), low-density lipoprotein cholesterol (CAD: OR, 1.55 [1.41–1.71]), high-density lipoprotein cholesterol (CAD: OR, 0.82 [0.74–0.91]), triglycerides (CAD: OR, 1.29 [1.14–1.45]), body mass index (CAD: OR, 1.25 [1.19–1.32]), and alcohol dependence (OR, 1.04 [1.03–1.06]) were causally related to CVD.ConclusionThis systematic MR study identified 11 modifiable factors as causal risk factors for CVD, indicating that these factors are important targets for preventing CVD.     

Circulating 25-hydroxy-vitamin D and the risk of cardiovascular diseases. Systematic review and meta-analysis of prospective cohort studies

AimsCirculating vitamin D is linked with the risk of cardiovascular disease (CVD). A meta-analysis has yet to explicitly explore correlation between vitamin D and the risk of CVD incidence and recurrent CVD. This meta-analysis examines the association between 25-hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and non-fatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483.Data synthesisA total of 79 studies (46 713 CVD cases in 1 397 831 participants) were included in the meta-analysis, of which 61 studies examined the risk of CVD incidence events, and 18 studies examined risk of recurrent CVD events. The risk of CVD incidence events (RR = 1.34, 95% CI: 1.26–1.43, p < 0.001) and recurrent CVD events (RR = 1.86, 95% CI: 1.46–2.36, p < 0.001) was higher in the lowest than the highest category of circulating 25(OH)D. Dose–response analysis reported a linear association for every 10 ng/ml increment of 25(OH)D and non-fatal CVD incidence events (RR = 0.94; 95% CI = 0.89–0.98, p = 0.005), lower fatal recurrent CVD events (RR = 0.45; 95% CI = 0.32–0.62, p < 0.001) and lower combined recurrent CVD events (RR = 0.80; 95% CI = 0.65–0.97, p = 0.023). A non-linear association was observed between higher 25(OH)D and lower fatal CVD incidence events (P-nonlinear<0.001), lower combined CVD incidence events (P-nonlinear = 0.001), and lower non-fatal recurrent CVD events (P-nonlinear = 0.044).ConclusionsThe lowest category of circulating 25(OH)D was associated with a higher risk of CVD incidence events and recurrent CVD events.     

Sedentary behavior and the risk of stroke: A systematic review and dose-response meta-analysis

Background and aimsThe sedentary behavior in people's daily life has continued to increase in recent years, causing many studies to focus on its relationship with diseases. Several studies have shown that sedentary behavior is an independent risk factor for cardiovascular disease and metabolic disease. Therefore, we performed a meta-analysis to assess the association between sedentary behavior and the risk of stroke.Methods and resultsTwo independent investigators searched for prospective cohort studies on the association between sedentary behavior and stroke risk, published before February 2022. We pooled adjusted effect size and performed the dose-response analysis by random-effect model. Seven studies with 677,614 participants and 15,135 stroke events during a median follow-up of 12.2 years were included. The pooled hazard ratio (HR) of stroke was 1.16 (95% confidence interval [CI]: 1.09–1.24) with no significant heterogeneity (I2 = 0.0%, p for heterogeneity = 0.983). In dose-response analysis, a nonlinear association between sedentary behavior and stroke risk was discovered. Stroke risk began to increase when sedentary time exceeded 3.7 h/d (HR, 1.01; 95% CI, 0.97–1.05). And when reached 11 h/d, a significantly increased risk of stroke was observed (HR, 1.21; 95% CI 1.12–1.31).ConclusionA nonlinear association was found in the dose-response analysis, with increased risk only when sedentary time exceeded a certain level. Further research is needed to explain the biological mechanisms by which sedentary time above a certain threshold significantly increases stroke risk. (PROSPERO registration number: CRD42022311544)     

Association of adherence to the dietary approach to stop hypertension and Mediterranean diets with blood pressure in a non-hypertensive population: Results from Isfahan Salt Study (ISS)

Background and aimsHypertension is among the major risk factors for cardiovascular events in the Iranian population. This cross-sectional study was designed to examine the association of adherence to the dietary approaches to stop hypertension (DASH) and Mediterranean (MED) dietary patterns with the distribution of blood pressure and pre-hypertension prevalence.Methods and resultsThis cross-sectional study was carried out in 1363 non-hypertensive adults. Adherence to the DASH and MED diets was calculated using a semi-quantitative food frequency questionnaire (FFQ). Hypertension was measured by the standard method. Multiple logistic regression was applied to obtain the odds ratio of pre-hypertension in the tertiles of MED and DASH dietary patterns. Compared to the lowest, participants with the highest adherence to the DASH dietary pattern had significantly lower systolic blood pressure (SBP) (111.3 ± 11.8 vs. 112.8 ± 12.5; P = 0.010) and diastolic blood pressure (DBP) (70.7 ± 9.2 vs. 71.8 ± 9.8; 0.042). There was no significant difference in the mean SBP and DBP among the participants across tertiles of MED or diet adherence. Higher scores of the DASH and MED diets were inversely associated with lower SBP after adjustment for all potential confounders (OR = ?0.04, 95% CI = ?0.29, ?0.01, P = 0.039) and (OR = ?0.04, 95% CI = ?0.72, ?0.02, P = 0.044), respectively. Also, DASH and MED dietary patterns was associated with reduced OR of pre-hypertension occurrence by 13% (OR: 0.87; 95% CI: 0.70–0.98; P for trend = 0.042) and 16% ([OR: 0.84; 95% CI: 0.69–0.97; P trend = 0.035), respectively.ConclusionAdherence to the DASH and MED diets was inversely associated with the odds for pre-hypertension and SBP.     

Patent Foramen Ovale Attributable Cryptogenic Embolism With Thrombophilia Has Higher Risk for Recurrence and Responds to Closure

ObjectivesThe aim of this study was to investigate the effect of management on the risk for recurrent events among patients with cryptogenic ischemic stroke or transient ischemic attack.BackgroundThe combination of patent foramen ovale (PFO) and hypercoagulability may greatly increase the risk for paradoxical embolism. However, previous randomized controlled trials evaluating the efficacy of PFO closure excluded these potential high-risk patients.MethodsPatients diagnosed with PFO attributable cryptogenic embolism were prospectively, without randomization, recruited from January 2005 to March 2018. The relationship between thrombophilia and recurrent events was evaluated in overall patients. Multivariate Cox regression was conducted to assess the relative risk for recurrence in PFO closure and medical therapy groups.ResultsA total of 591 patients with cryptogenic embolism with PFO were identified. The median duration of follow-up was 53 months, and thrombophilia significantly increased the risk for recurrent events (hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.09 to 3.16; p = 0.024). PFO closure was superior to medical therapy in overall patients (HR: 0.16; 95% CI: 0.09 to 0.30; p < 0.001). Of the 134 patients (22.7%) with thrombophilia, there was a difference in the risk for recurrence events between the PFO closure (6 of 89) and medical therapy (15 of 45) groups (HR: 0.25; 95% CI: 0.08 to 0.74; p = 0.012). There was no potential heterogeneity in the further subgroup analysis.ConclusionsPatients with cryptogenic stroke with PFO and hypercoagulable state had increased risk for recurrent stroke or transient ischemic attack. PFO closure provided a lower risk for recurrent events compared with medical therapy alone.     

Basal interventricular septum thinning and long-term left ventricular function in patients with sarcoidosis

BackgroundBasal interventricular septum (IVS) thinning on transthoracic echocardiography (TTE) is highly specific to cardiac sarcoidosis. Although basal IVS thinning is listed as one of the five major diagnostic criteria for cardiac sarcoidosis, its association with long-term cardiac function has not been investigated. This study aimed to evaluate the epidemiology and clinical relevance of basal IVS thinning in a clinic-based cohort of patients with sarcoidosis.MethodsThis retrospective observational study was conducted at a general sarcoidosis clinic. The incidence of basal IVS thinning and associations with variables at baseline and a delayed onset of left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < 50%) were analyzed.ResultsOf the 1009 patients, 23 (2.3%) had basal IVS thinning. Basal IVS thinning was associated with cardiac pacemaker (PM) implantation at baseline (adjusted odds ratio = 20.5; 95% confidence interval [CI] = 7.9–53.2; P < 0.01). Of the 768 patients with an LVEF of ≥50% at baseline who underwent one or more longitudinal TTEs after baseline, 36 (4.7%) developed LV dysfunction over a median observation period of 88.9 months. Basal IVS thinning and PM implantation at baseline were the independent predictors of a delayed onset of LV dysfunction (basal IVS thinning, adjusted hazard ratio [HR] = 3.7; 95% CI = 1.5–9.6; PM implantation, adjusted HR = 15.7; 95% CI = 7.4–33.3).ConclusionsBasal IVS thinning in patients with sarcoidosis can predict a delayed onset of LV dysfunction even when the LV function is preserved at the time of detection.     

Diets high in glycemic index and glycemic load are associated with an increased risk of metabolic syndrome among Korean women

Background and aimsAccurate estimation of the glycemic index (GI) and glycemic load (GL) of diets is essential when assessing health implications of dietary GI and GL. The present study aimed to estimate dietary GI and GL utilizing the updated GI tables with a large number of new, reliable GI values and assess their associations with metabolic syndrome among Korean adults.Methods and resultsWe analyzed data from 3317 men and 6191 women for this cross-sectional study. Dietary intake was assessed with a validated food frequency questionnaire. Metabolic syndrome and its components were defined based on the harmonized criteria with Korean-specific cutoffs for waist circumference. Multivariate logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with women in the lowest quintiles of energy-adjusted dietary GI and GL, women in the highest quintiles had significantly greater risks of metabolic syndrome (GI, OR = 1.56, 95% CI = 1.18–2.06; GL, OR = 1.80, 95% CI = 1.27–2.57), elevated blood pressure, reduced high-density lipoprotein cholesterol (HDL-C, both GI and GL), elevated triglycerides (GI only), elevated waist circumference, and elevated fasting glucose (GL only). Among men, no significant association was noted except for a higher risk of reduced HDL-C (OR = 1.59, 95% CI = 1.01–2.29) in the highest quintile of energy-adjusted dietary GI than in the lowest quintile.ConclusionOur findings suggest that dietary GI and GL are positively associated with metabolic syndrome risk among women, but not men, in Korea.     

Plasma l-carnitine and risks of cardiovascular events and recurrent stroke after ischemic stroke: A nested case-control study

Background and aimsl-Carnitine was suggested to prevent the progression of atherosclerosis, myocardial and neurologic injury, and exhibited cardioprotective effects. However, epidemiological data on circulating l-carnitine and risks of cardiovascular events in the setting of stroke is rare. We aimed to explore the relationships between plasma l-carnitine and cardiovascular events and stroke recurrence after ischemic stroke in a nested case-control study.Methods and resultsA total of 323 cardiovascular events (including 264 recurrent strokes) and 323 matched controls (free of recurrent cardiovascular events) were included. Study outcomes included cardiovascular events and recurrent stroke after ischemic stroke. Plasma l-carnitine concentrations were measured by ultra-high-performance LC-MS/MS. Conditional logistic regression models were used to estimate odds ratios (ORs) of stroke outcomes. Plasma l-carnitine was inversely associated with cardiovascular events (OR = 0.69, 95% CI: 0.57–0.84 per SD) and recurrent stroke (OR = 0.72, 95% CI: 0.58–0.88 per SD) after adjusting for established risk confounders. Compared with the lowest tertile of l-carnitine, adjusted ORs of cardiovascular events and recurrent stroke for participants in the highest tertiles were 0.35 (95% CI: 0.21–0.57) and 0.36 (95% CI: 0.21–0.62), respectively. In addition, l-carnitine provided incremental predictive ability beyond established risk factors, shown by increase in C statistics, net reclassification improvement and integrated discrimination improvement.ConclusionsHigher l-carnitine levels were associated with lower risks of cardiovascular events and recurrent stroke after ischemic stroke. Our findings provided evidence supporting plasma l-carnitine as a potential prognostic marker in risk discrimination and stratification in patients with ischemic stroke.Trial registrationClinicaltrials.gov as NCT01840072. URL: https://www.clinicaltrials.gov.     

Statins and risk of venous thromboembolic diseases: A two-sample mendelian randomization study

Background and aimsIn observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal.Methods and resultsData on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio [OR]: 0.999, 95% CI: 0.998–1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999–1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999–1.000, P = 0.008).ConclusionOur findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.     

Clinical Outcomes Associated With Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulation in Atrial Fibrillation

ObjectivesThis study sought to investigate clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulants (DOACs) in patients with high-risk atrial fibrillation (AF).BackgroundLAAO has been shown to be noninferior to warfarin for stroke prevention in AF. However, anticoagulation with DOACs is now preferred over warfarin as thromboprophylaxis in AF.MethodsPatients with AF enrolled in the Amulet Observational Registry (n = 1,088) who had successful LAAO with the Amplatzer Amulet device (n = 1,078) were compared with a propensity score–matched control cohort of incident AF patients (n = 1,184) treated by DOACs identified from Danish national patient registries. Propensity score matching was based on the covariates of the CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65–74 years, sex category) and HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores for predicting stroke and bleeding. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium ≥3), or all-cause mortality, and follow-up was 2 years.ResultsAF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients treated with DOACs (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.49 to 0.67). Total events and event rates per 100 patient-years were (LAAO vs. DOACs) 256 vs. 461 and 14.5 vs. 25.7, respectively. The risk of ischemic stroke was comparable between groups (HR: 1.11; 95% CI: 0.71 to 1.75), while risk of major bleeding (HR: 0.62; 95% CI: 0.49 to 0.79) and all-cause mortality (HR: 0.53; 95% CI: 0.43 to 0.64) were significantly lower in patients treated with LAAO.ConclusionsAmong high-risk AF patients, LAAO in comparison with DOACs may have similar stroke prevention efficacy but lower risk of major bleeding and mortality.     

Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients

BackgroundThe COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease.ObjectivesThis study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in “COMPASS-eligible” patients.MethodsKey COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion).ResultsPatients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]).ConclusionsIn a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin.     

Clinical Outcomes of On-Site Versus Off-Site Endovascular Stroke Interventions

ObjectivesThe aim of this study was to assess whether offering local endovascular stroke therapy (EST) rather than transferring patients off-site to receive EST would improve outcomes.BackgroundThere are limited data to determine whether offering EST on-site rather than transferring patients to receive EST off-site improves clinical outcomes.MethodsA large academic consortium database was queried to identify patients with acute ischemic stroke who received EST between October 2015 and September 2019. Primary endpoints were in-hospital mortality and poor functional outcomes. Secondary endpoints were major complications, length of stay, and cost. Baseline characteristics were adjusted for using propensity score matching and multivariate risk adjustment.ResultsA total of 22,193 patients with acute ischemic stroke who underwent EST (50.8% on-site, 49.2% off-site) were included. Mean ages were 67.9 ± 15.5 years and 68.4 ± 15.5 years, respectively (p = 0.03). In the propensity score matching analysis, mortality and poor functional outcomes were higher in the off-site EST group (14.7% vs. 11.2% and 40.7% vs. 35.9%, respectively; p < 0.001). In the risk-adjusted analyses with different models, in-hospital mortality and poor functional outcomes remained significantly higher in the off-site EST group. In the most comprehensive model (adjusting for age, sex, demographics, risk factors, tissue plasminogen activator use, and institutional EST volume), in-hospital mortality and poor functional outcomes were significantly higher in the off-site EST group, with odds ratios of 1.38 (95% confidence interval: 1.26 to 1.51) and 1.26 (95% confidence interval: 1.18 to 1.34), respectively (p < 0.001). The incidence of intracranial hemorrhage and mechanical ventilation was higher in the off-site group, but cost was higher in the on-site group in both the propensity score matching and risk-adjusted analyses.ConclusionsIn contemporary U.S. practice, patients with acute ischemic stroke treated with EST on-site had lower in-hospital mortality and better functional outcomes compared with those transferred off-site for EST.     

Incidence,Characterization, and Clinical Impact of Device-Related Thrombus Following Left Atrial Appendage Occlusion in the Prospective Global AMPLATZER Amulet Observational Study

ObjectivesThis study sought to report the incidence, characteristics, and clinical impact of device-related thrombus (DRT) following left atrial appendage occlusion (LAAO) with the AMPLATZER Amulet device (Abbott, Plymouth, Minnesota).BackgroundDRT is a potential serious complication of LAAO, but the incidence and clinical impact of DRTs in a real-world setting are not well characterized.MethodsA total of 1,088 patients were enrolled in a multicenter prospective study and followed for 1 year. All events were adjudicated by an independent committee, including the presence of DRT. Patients with DRT were reviewed for suboptimal device implantation and characterization of DRT formation. Multiple Cox regression was performed to identify predictors of DRT formation.ResultsDevice implantation was successful in 1,078 (99%) patients, with 1-year follow-up completed in 96.3% of patients. A total of 18 DRTs occurred in 17 patients (1.7%/year), as a second DRT developed following complete resolution of an initial DRT in 1 patient. The left upper pulmonary vein ridge was not covered by the Amulet disc in 82% of DRT patients, indicating suboptimal implantation, with most thrombus developing in the untrabeculated area of the LAA ostium between the pulmonary vein ridge and the upper edge of the disc. Three (18%) DRT patients had an ischemic stroke, all within 3 months of DRT diagnosis. Patients with a DRT were at a greater risk for ischemic stroke or transient ischemic attack compared with non-DRT patients (hazard ratio: 5.27; 95% confidence interval: 1.58 to 17.55; p = 0.007). Larger LAA orifice width was a predictor of DRT formation (hazard ratio: 1.09; 95% confidence interval: 1.00 to 1.19; p = 0.04).ConclusionsFollowing LAAO with the AMPLATZER Amulet device, DRT was observed infrequently. Although the presence of DRT was associated with an increased rate of ischemic stroke or transient ischemic attack as compared with patients without DRT, the large majority of DRT patients (82%) did not experience any ischemic neurologic events.     

MAFLD is associated with increased all-cause mortality in low cardiovascular-risk individuals but not in intermediate to high-risk individuals

Background and aimsMetabolic-associated fatty liver disease (MAFLD) is increasingly recognized as a systematic disease rather than just a liver disease alone, which raises concerns about its long-term impact on different populations. This study aimed to clarify the effects of MAFLD on long-term outcomes among different cardiovascular risk-stratified populations.Methods and resultsEligible individuals in the Third National Health and Nutrition Examination Surveys (NHANES Ⅲ, 1988–1994) were enrolled. Participants were classified into low, intermediate, or high cardiovascular-risk populations according to the Framingham general equations. Kaplan-Meier survival analysis and Cox regression models were used to investigate the association between MAFLD and long-term outcomes in different cardiovascular-risk populations.A total of 8897 adults were enrolled in the final analysis. The median ages in the non-MAFLD and MAFLD groups were 44 and 49 years old, respectively. During a median follow-up of 22.8 years, a total of 2991 deaths were recorded, including 1694 deaths (30.3%) in non-MAFLD and 1297 deaths (39.2%) in MAFLD (P < 0.001). In the low cardiovascular-risk population, MAFLD individuals had increased all-cause mortality than non-MAFLD individuals (HR = 1.206, 95% CI:1.0338-1.400, P = 0.014). However, similar results were not observed in intermediate or high-cardiovascular-risk individuals. Further analysis of cause-specific mortality suggested that MAFLD was associated with higher cancer-related mortality in the low-risk population (HR = 1.313, 95% CI:1.000-1.725, P = 0.049).ConclusionsMAFLD was associated with increased all-cause mortality among individuals with low cardiovascular risk, rather than those with an intermediate or high cardiovascular risk.