No association between alcohol consumption and risk of atrial fibrillation: A two-sample Mendelian randomization study

Background and aimsAlthough many observational studies have suggested that alcohol intake was associated with incident atrial fibrillation (AF), controversy remains. This study aimed to examine the causal association of alcohol intake with the risk of AF.Methods and resultsTwo-sample Mendelian randomization (MR) analysis was performed to estimate the causal effects of alcohol consumption, alcohol dependence, or alcohol use disorder identification test (AUDIT) scores on AF. Summary data on single nucleotide polymorphisms (SNPs) associated with AF were obtained from a genome-wide association study (GWAS) with up to 1,030,836 participants. The fixed- and random-effect inverse-variance weighted (IVW) methods were used to calculate the overall causal effects. MR analysis revealed nonsignificant association of genetically predicted alcohol consumption with risk of AF using fixed- and random-effect IVW approaches (odds ratio (OR) [95% confidence interval (CI)] = 1.004 [0.796–1.266], P = 0.975; OR [95% CI] = 1.004 [0.766–1.315], P = 0.979). Genetically predicted alcohol dependence was also not causally associated with AF in the fixed- and random-effect IVW analyses (OR [95% CI] = 1.012 [0.978–1.048], P = 0.490; OR [95% CI] = 1.012 [0.991–1.034], P = 0.260). There was no significantly causal association between AUDIT and AF in the fixed- and random-effect IVW analyses (OR [95% CI] = 0.889 [0.433–1.822], P = 0.748; OR [95% CI] = 0.889 [0.309–2.555], P = 0.827). Sensitivity analyses indicated no evidence of pleiotropy and heterogeneity in statistical models.ConclusionsThis MR study did not find evidence of a causal association between alcohol intake and AF.     

Association between dairy product consumption and hyperuricemia in an elderly population with metabolic syndrome

Background and aimsThe prevalence of hyperuricemia has increased substantially in recent decades. It has been suggested that it is an independent risk factor for weight gain, hypertension, hypertriglyceridemia, metabolic syndrome (MetS), and cardiovascular disease. Results from epidemiological studies conducted in different study populations have suggested that high consumption of dairy products is associated with a lower risk of developing hyperuricemia. However, this association is still unclear. The aim of the present study is to explore the association of the consumption of total dairy products and their subtypes with the risk of hyperuricemia in an elderly Mediterranean population with MetS.Methods and resultsBaseline cross-sectional analyses were conducted on 6329 men/women (mean age 65 years) with overweight/obesity and MetS from the PREDIMED-Plus cohort. Dairy consumption was assessed using a food frequency questionnaire. Multivariable-adjusted Cox regressions were fitted to analyze the association of quartiles of consumption of total dairy products and their subtypes with the prevalence of hyperuricemia. Participants in the upper quartile of the consumption of total dairy products (multiadjusted prevalence ratio (PR) = 0.84; 95% CI: 0.75–0.94; P-trend 0.02), low-fat dairy products (PR = 0.79; 95% CI: 0.70–0.89; P-trend <0.001), total milk (PR = 0.81; 95% CI: 0.73–0.90; P-trend<0.001), low-fat milk (PR = 0.80; 95% CI: 0.72–0.89; P-trend<0.001, respectively), low-fat yogurt (PR = 0.89; 95% CI: 0.80–0.98; P-trend 0.051), and cheese (PR = 0.86; 95% CI: 0.77–0.96; P-trend 0.003) presented a lower prevalence of hyperuricemia. Whole-fat dairy, fermented dairy, and yogurt consumption were not associated with hyperuricemia.ConclusionsHigh consumption of total dairy products, total milk, low-fat dairy products, low-fat milk, low-fat yogurt, and cheese is associated with a lower risk of hyperuricemia.     

Relationship between alcohol consumption and insulin resistance measured using the homeostatic model assessment for insulin resistance: A retrospective cohort study of 280,194 people

Background and aimAlcohol consumption causes metabolic disorders and is a known risk factor for cardiovascular disease. However, some studies suggested that low level alcohol consumption improves insulin resistance. We evaluated the effects of alcohol consumption on insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR).Methods and resultsThis study included 280,194 people without diabetes who underwent comprehensive health examinations more than twice between 2011 and 2018. The levels of alcohol intake were obtained through a self-questionnaire. All subjects were divided into two groups based on the Korean standard cut-off value of HOMA-IR, 2.2. Cox proportional hazard analysis was used to assess the risk of insulin resistance according to alcohol consumption. The mean age of the study subjects was 38.2 years and 55.7% were men. During the follow-up period (median 4.13 years), HOMA-IR progressed from <2.2 to ≥2.2 in 64,443 subjects (23.0%) and improved from ≥2.2 to <2.2 in 21,673 subjects (7.7%). In the parametric survival analysis, alcohol consumption was associated with improvement of HOMA-IR (HR [95% CI], 1.09[1.03–1.14], 1.11[1.06–1.17] and 1.20[1.13–1.26], respectively). In the analysis classified according to changes in alcohol consumption amounts, increased alcohol consumption tended to prevent the progression of HOMA-IR (0.97[0.96–0.99]; p = 0.004). However, the association between the changes in alcohol consumption amounts and improvement of HOMA-IR was not statistically significant.ConclusionThis retrospective observational study has shown that alcohol consumption can improve insulin resistance and increased alcohol consumption amounts may have preventive effects on the progression of HOMA-IR compared to the baseline level.     

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.     

Screen time and the risk of metabolic syndrome among children and adolescents: A systematic review and dose-response meta-analysis

AimsThe metabolic syndrome (MetS) and its consequences are one of the main public health challenges worldwide. We conducted a systematic review and dose-response meta-analysis of studies that examined the association between screen time and the MetS among children and adolescents.Data synthesisA systematic search was conducted using electronic databases, including PubMed, Scopus, ProQuest, and Cochrane Library, for studies published from 1963 up to 2 May 2022. In this systematic review and meta-analysis, observational studies with cross-sectional, case-control, and cohort design evaluating the association between screen time and MetS were included. Random effects models and linear and nonlinear dose-response meta-analyses were used to pool study results.ResultsSeven studies were included in the meta-analysis. The summary OR of MetS among children and adolescents for the highest vs. lowest time of screen time was 1.64 (95% CI: 1.32–2.03, with little evidence of heterogeneity, I² = 9.3%, P-_{heterogeneity} = 0.35, n = 7 studies) and 1.64 (95% CI: 1.27–2.12, I² = 27.7%, n = 6) for cross-sectional studies. Results persisted across several additional subgroup analyses. There was a linear positive association between screen time and the risk of MetS (P dose-response < 0.0001; P nonlinearity = 0.64) with an OR of 1.29 (95% CI: 1.12–1.46) per 2 h/day increment in screen time.ConclusionThe current dose-response meta-analysis suggested that increased screen time is associated with an increased risk of MetS among children and adolescents. Public health strategies may target unhealthy screen-based related behaviors to halt the development of MetS among children and adolescents.     

Dietary acid load and risk of hypertension: A systematic review and dose-response meta-analysis of observational studies

Background and aimPrevious studies have assessed diet-induced mild metabolic acidosis in relation to blood pressure, however, data are conflicting. Current systematic review and dose-response meta-analysis aimed to summarize earlier findings from observational studies on the association between dietary acid load and hypertension.Methods and resultsWe searched the online databases for relevant publications up to Feb 2019, using relevant keywords. Overall, 14 studies (3 prospective and 11 cross-sectional studies) that included 306,183 individuals and 62,264 cases of hypertension were included in the current meta-analysis. Combining effect sizes from both prospective and cross-sectional studies revealed no significant non-linear association between dietary acid load (based on net endogenous acid production (NEAP) method) and hypertension. However, stratified analysis based on study design showed a significant non-linear association between dietary acid load and hypertension in prospective studies (P = 0.006), but not cross-sectional ones. According to linear dose-response analysis, no significant association was found between dietary acid load (based on NEAP) and hypertension (combined effect size: 1.01, 95% CI: 0.97–1.06, P = 0.51). In terms of dietary acid load based on potential renal acid load (PRAL) method, no significant non-linear association was seen with hypertension (P = 0.52). However, in linear dose-response analysis, a-20 unit increase in PRAL values was associated with 3% increased risk of hypertension (combined effect size: 1.03, 95% CI: 1.00–1.06, P = 0.03).ConclusionWe found a significant positive association between dietary acid load and hypertension. Further studies, particularly those with prospective nature, are needed to confirm our findings.     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Exposure to Chinese famine in early life modifies the association between hyperglycaemia and cardiovascular disease

Background and aimsThe Great Leap Forward Famine during 1959–1961 was the world's largest famine, and its adverse long-term effects might be more apparent in the coming decade with ageing of the exposed populations. The aim of this study was to examine whether the Chinese Famine modified the effect of hyperglycaemia on cardiovascular disease (CVD).Methods and resultsWe used data of 4337 adults born between 1952 and 1964 collected from the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression was used to estimate the odds ratios (ORs) and confidence intervals (CIs) between hyperglycaemia and CVD. The prevalence of CVD showed significant difference among different famine exposure cohorts (P = 0.0156). After multivariable adjustment, the ORs (95% CIs) were as follows: 1.46 (0.94, 2.26) for late childhood, 1.76 (1.06, 2.90) for mid childhood, 1.40 (0.86, 2.27) for early childhood, 2.55 (1.30, 5.02) for the foetal cohort and 1.10 (0.63, 1.95) for the non-exposed cohort. There was a significant interaction between hyperglycaemia and famine exposure for CVD (P = 0.0374). In addition, the subgroup analyses showed that the effect of hyperglycaemia on CVD in the foetal exposure cohort was significantly higher than those in any of the other famine-exposed cohorts, especially in those who lived in rural areas (OR: 4.67, 95% CI: 1.70–12.84), those who lived in severe famine areas (OR: 5.01, 95% CI: 1.22–20.66) and those who were men (OR: 3.66, 95% CI: 1.01–13.33).ConclusionExposure to the Chinese Famine, especially during the foetal stage of life, aggravated the association between hyperglycaemia and CVD.     

Genetically Predicted Adiposity,Diabetes, and Lifestyle Factors in Relation to Diverticular Disease

Background & AimsAdiposity, type 2 diabetes, alcohol and coffee consumption, and smoking have been examined in relation to diverticular disease in observational studies. We conducted a Mendelian randomization study to assess the causality of these associations.MethodsIndependent genetic instruments associated with the studied exposures at genome-wide significance were obtained from published genome-wide association studies. Summary-level data for the exposure-associated single nucleotide polymorphisms with diverticular disease were available in the FinnGen consortium (10,978 cases and 149,001 noncases) and the UK Biobank study (12,662 cases and 348,532 noncases).ResultsHigher genetically predicted body mass index and genetic liability to type 2 diabetes and smoking initiation were associated with an increased risk of diverticular disease in meta-analyses of results from the two studies. The combined odds ratio of diverticular disease was 1.23 (95% confidence interval [CI], 1.14–1.33; P < .001) for a 1-standard deviation (~4.8 kg/m²) increase in body mass index, 1.04 (95% CI, 1.01–1.07; P = .007) for a 1-unit increase in log-transformed odds ratio of type 2 diabetes, and 1.21 (95% CI, 1.12–1.30; P < .001) for a 1-standard deviation increase in prevalence of smoking initiation. Coffee consumption was not associated with diverticular disease, whereas the association for alcohol consumption largely differed between the 2 studies.ConclusionsThis study strengthens the causal associations of higher body mass index, type 2 diabetes, and smoking with an increased risk of diverticular disease. Coffee consumption is not associated with diverticular disease. Whether alcohol consumption affects the risk of diverticular disease needs further investigation.     

Lipid profiles and the risk of new-onset hypertension in a Chinese community-based cohort

Background and aimsDyslipidemia and hypertension, key risk factors for cardiovascular disease, may share similar pathophysiological processes. A longitudinal association was reported between dyslipidemia and new-onset hypertension, but few data were published in Asian. We aimed to investigate the association of lipid profiles with new-onset hypertension in a Chinese community-based non-hypertensive cohort without lipid-lowering treatment (n = 1802).Methods and resultsNew-onset hypertension was defined as any self-reported history of hypertension, systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg, or receiving antihypertensive medications at follow-up. Logistic regression models were used to evaluate the associations. Participants were aged 53.97 ± 7.49 years, 31.19% were men, and 64.54% with dyslipidemia. During a median of 2.30 years follow-up, the incidence of new-onset hypertension was 12.99%. Multivariate adjusted risks of new-onset hypertension increased with triglyceride increases (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.03–1.27) and high-density lipoprotein cholesterol (HDL-C) decreases (OR = 0.47, 95% CI: 0.29–0.76) for one unit. However, threshold effects were observed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C. Compared with subjects with hyperlipidemia, in those with normal concentrations of TC, LDL-C, and non-HDL-C increased risks of new-onset hypertension were observed with OR (95% CI) of 1.65 (1.10–2.46), 1.58 (1.07–2.33), and 1.57 (1.15–2.15) for one unit increasement, respectively, after adjusting for all covariates.ConclusionHigher TG and lower HDL-C increased the risk of new-onset hypertension, but for TC, LDL-C and non-HDLC, the risk of new-onset hypertension was increased only at normal concentrations in a Chinese community-based cohort.     

Thrombotic Risk and Cardiovascular Events in Patients With Revascularization Deferral After Fractional Flow Reserve Assessment

ObjectivesThe aim of this study was to evaluate the impact of thrombotic risk on the occurrence of cardiovascular events in patients with coronary artery disease with deferred revascularization after fractional flow reserve (FFR) measurements.BackgroundDeferral of revascularization on the basis of FFR is generally considered to be safe, but after deferral, some patients have cardiovascular events over time.MethodsFrom J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1,263 patients with deferral of revascularization on the basis of FFR were evaluated. The association between thrombotic risk as assessed by CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) thrombotic score and 5-year target vessel failure (TVF) and major adverse cardiac and cerebrovascular events (MACCE) was investigated.ResultsFFR and high thrombotic risk (HTR) were associated with increased risk for 5-year TVF (FFR per 0.01-unit decrease: HR: 1.08; 95% CI: 1.05-1.11; P < 0.001; HTR: HR: 2.16; 95% CI: 1.37-3.39; P < 0.001) and MACCE (FFR per 0.01-unit decrease: HR: 1.05; 95% CI: 1.02-1.06; P < 0.001; HTR: HR: 2.11; 95% CI: 1.56-2.84; P = 0.001). Patients with HTR had higher risk for 5-year TVF (HR: 2.30; 95% CI: 1.45-3.66; P < 0.001) and MACCE (HR: 2.34; 95% CI: 1.75-3.13; P < 0.001) than those without HTR, even when they had negative FFR.ConclusionsAssessment of thrombotic risk provides additional prognostic value to FFR in predicting 5-year TVF and MACCE in patients with deferral of revascularization after FFR measurements. (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry; UMIN000014473)     

Increased visceral fat accumulation modifies the effect of insulin resistance on arterial stiffness and hypertension risk

Background and aimsBoth insulin resistance (IR) and visceral adipose tissue (VAT) are related cardiometabolic risk factors; nevertheless, their joint effect on endothelial functionality is controversial. This study aims to evaluate the joint effect of IR and VAT on endothelial functionality using the pulse-waveform analysis and explore the mediating role of VAT on the effect of IR on arterial pressure, arterial stiffness and incident arterial hypertension.Methods and resultsWe measured VAT (n = 586) using two methods (dual-energy X-ray absorptiometry and a clinical surrogate), arterial stiffness (with pulse-waveform velocity), and IR (using three methods: HOMA2-IR (n = 586), a frequently sampled intravenous glucose tolerance test (n = 131) and euglycemic hyperinsulinemic clamping (n = 97)) to confirm the mediator effect of IR on VAT. The incidence of arterial hypertension attributable to the mediating effect of IR related to VAT was evaluated using a prospective cohort (n = 6850). Adjusted linear regression models, causal mediation analysis, and Cox-proportional hazard risk regression models were performed to test our objective. IR and VAT led to increased arterial stiffness and increased blood pressure; the combination of both further worsened vascular parameters. Nearly, 57% (Δ_E→MY 95% CI: 31.7–100.0) of the effect of IR on altered pulse-wave velocity (PWV) analysis was mediated through VAT. Moreover, VAT acts as a mediator of the effect of IR on increased mean arterial pressure (Δ_E→MY 35.7%, 95% CI: 23.8–59) and increased hypertension risk (Δ_E→MY 69.1%, 95% CI: 46.1–78.8).ConclusionVAT acts as a mediator of IR in promoting arterial stiffness and arterial hypertension. Both phenomena should be targeted to ameliorate the cardiometabolic risk.     

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.     

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.     

Moderate and heavy alcohol consumption are prospectively associated with decreased left ventricular ejection fraction: The Hoorn Study

Background and aimsData on the prospective relationship of alcohol consumption at more moderate levels with systolic and diastolic function are scarce. We aimed to examine the prospective association of alcohol consumption with echocardiographic measures of cardiac structure and function, in individuals with and without type 2 diabetes (T2DM).Methods and resultsWe included 778 participants from the Hoorn Study (aged 68.4 ± 7.2 years, 49% women), a population-based prospective cohort study, oversampled for people with impaired glucose metabolism or T2DM. Self-reported alcohol consumption was collected at baseline with a validated food-frequency questionnaire and categorized into: none (0/week), light (>0-≤30 g/week), light-to-moderate (>30-≤70 g/week), moderate (>70-≤140 g/week), and heavy drinkers (>140 g/week). Echocardiography was performed at baseline (N = 778) and after 8 years follow-up (N = 404). Multiple linear regression was used to study the association between alcohol consumption and echocardiographic measures (left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI)), adjusted for confounders. Moderate and heavy alcohol consumption were associated with a decreased LVEF of −3.91% (CI: −7.13;-0.69) for moderate and −4.77% (−8.18;-1.36) for heavy drinkers compared to light drinkers. No associations were found between alcohol consumption, LVMI and LAVI. Modified Poisson regression showed a trend that higher alcohol consumption amounts were associated with a higher risk of incident systolic dysfunction (LVEF≤50%) (P-for-trend 0.058).ConclusionThe findings provide longitudinal evidence that moderate and heavy alcohol consumption are associated with decreased LVEF and trend towards a higher risk of incident LV systolic dysfunction, compared to light drinkers.     

Low vitamin D levels predict left atrial thrombus in nonvalvular atrial fibrillation

Background and aimsWe determined the association between left atrial (LA) thrombus occurrence and a non-classic risk marker, plasma levels of vitamin D, in atrial fibrillation (AF) patients on continuous non-vitamin K antagonist oral anticoagulant (NOAC) therapy for ≥4 weeks. Low levels of plasma 25-hydroxy vitamin D (25-OHD) are predictive of fatal stroke. Vitamin D has anticoagulant effects on the coagulation cascade, which are indirectly targeted by NOAC therapy. The impact of plasma levels of vitamin D on the rate of LA thrombus detected by transesophageal echocardiography (TEE) in AF patients is unknown.Methods and resultsWe enrolled 201 (133 female) AF patients who were using continuous NOAC therapy for ≥4 weeks. All patients underwent transthoracic and TEE examination. Serum concentrations of 25-OHD, C-reactive protein (CRP) levels, CHA₂DS₂-VASc scores and parameters, LA size, and left ventricle ejection fraction (LVEF) were examined before the TEE procedure. LA thrombus occurrence was independently associated with serum levels of 25-OHD (OR: 0.884; 95% CI: 0.839–0.932; P < 0.001), LA diameter (OR: 1.120; 95% CI: 1.038–1.209; P = 0.003), and LVEF(OR: 0.944; 95% CI: 0.896–0.995; P = 0.032). Dense spontaneous echo contrast (SEC) presence was also inversely associated with 25-OHD concentrations.ConclusionsLow 25-OHD levels, as a non-classic risk factor, were independently and significantly associated with dense SEC and LA thrombus occurrence in AF patients under NOAC therapy, as well as LA enlargement and decreased LVEF. Further large-scale studies are needed to explain the role of vitamin D deficiency, or efficacy of replacement, on LA thrombus occurrence.     

Half-Dose Direct Oral Anticoagulation Versus Standard Antithrombotic Therapy After Left Atrial Appendage Occlusion

ObjectivesThis study evaluated the long-term efficacy of a standard antithrombotic strategy versus half-dose direct oral anticoagulation (DOAC) after Watchman implantation.BackgroundNo consensus currently exists on the selection of the most effective antithrombotic strategy to prevent device-related thrombosis (DRT) in patients undergoing endocardial left atrial appendage closure.MethodsAfter successful left atrial appendage closure, consecutive patients were prescribed a standard antithrombotic strategy (SAT) or long-term half-dose DOAC (hdDOAC). The primary composite endpoint was DRT and thromboembolic (TE) and bleeding events.ResultsOverall, 555 patients (mean age 75 ± 8 years, 63% male; median 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] score 4 [interquartile range (IQR): 3-6]; median HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] score 3 [IQR: 2-4]) were included. Patients were categorized into 2 groups (SAT: n = 357 vs hdDOAC: n = 198). Baseline clinical characteristics were similar between groups. The median follow-up duration was 13 months (IQR: 12-15 months). DRT occurred in 12 (2.1%) patients, all in the SAT group (3.4% vs 0.0%; log-rank P = 0.009). The risk of nonprocedural major bleeding was significantly more favorable in the hdDOAC group (0.5% vs. 3.9%; log-rank P = 0.018). The rate of the primary composite endpoint of DRT and TE and major bleeding events was 9.5% in SAT patients and 1.0% in hdDOAC patients (HR: 9.8; 95% CI: 2.3-40.7; P = 0.002).ConclusionsAfter successful Watchman implantation, long-term half-dose DOAC significantly reduced the risk of the composite endpoint of DRT and TE and major bleeding events compared with a standard, antiplatelet-based, antithrombotic therapy.     

Association of elective cesarean delivery with metabolic measures in childhood: A prospective cohort study in China

Background and aimsCesarean delivery may increase the risk of childhood obesity, a precursor of metabolic syndrome (MetS). We aimed to investigate the association of elective cesarean delivery (ElCD) with MetS and its components in a Chinese birth cohort.Methods and resultsThis cohort included 1467 children (737 delivered by ElCD and 730 by spontaneous vaginal delivery [SVD]) who were followed up at the age of 4–7 years in 2013. MetS was defined as the presence of ≥3 components: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL), high fasting glucose, and hypertension. Of the 1467 children, 93 (6.3%) were categorized as having MetS: 50 (6.8%) delivered by ElCD and 43 (5.9%) by SVD. After multivariable adjustment, ElCD was not associated with MetS (adjusted odds ratio [AOR] 1.15, 95% confidence interval [CI] 0.74, 1.78) or certain components including hypertriglyceridemia, low HDL, and high fasting glucose but was associated with central obesity (AOR 1.33, 95% CI 1.02, 1.72) and hypertension (AOR 1.50, 95% CI 1.15, 1.96), as well as higher levels of total cholesterol (3.43 vs. 3.04 mmol/L; P < 0.001), low-density lipoprotein–cholesterol (1.77 vs. 1.67 mmol/L, P = 0.002), fasting glucose (5.08 vs. 5.02 mmol/L, P = 0.022), systolic (97.57 vs. 94.69 mmHg, P < 0.001)/diastolic blood pressure (63.72 vs. 62.24 mmHg, P < 0.001), and BMI (15.46 vs. 14.83 kg/m², P < 0.001) than SVD.ConclusionsElCD is not associated with MetS in early to middle childhood but is associated with its components including central obesity and hypertension, as well as various continuous indices.     

Association between body mass index and mortality in atrial fibrillation patients with and without diabetes mellitus: Insights from a multicenter registry study in China

Background and aimsThe aim of this study was to evaluate the association between body mass index (BMI) and mortality in atrial fibrillation (AF) patients with and without diabetes mellitus (DM).Methods and resultsA total of 1991 AF patients were enrolled and divided into two groups according to whether they have DM at recruitment. Baseline information was collected and a mean follow-up of 1 year was carried out. The primary outcome was defined as all-cause mortality with the secondary outcomes including cardiovascular mortality, stroke and major adverse events (MAEs). Univariable and multivariable Cox regression were performed to estimate the association between BMI and 1-year outcomes in AF patients with and without DM. 309 patients with AF (15.5%) had comorbid DM at baseline. Patients with DM were more likely to have cardiovascular comorbidities, receive relevant medications but carry worse 1-year outcomes. Multivariable Cox regressions indicated that elevated BMI was related with reduced risk of all-cause mortality, cardiovascular mortality and major adverse events. Compared to normal weight, overweight [HR (95% CI): 0.548 (0.405–0.741), p < 0.001] and obesity [HR (95% CI): 0.541 (0.326–0.898), p = 0.018] were significantly related with decreased all-cause mortality for the entire cohort. Remarkably reduced all-cause mortality in the overweight [HR (95% CI): 0.497 (0.347–0.711), p < 0.001] and obesity groups [HR (95% CI): 0.405 (0.205–0.800), p = 0.009] could also be detected in AF patients without DM, but not in those with DM.ConclusionElevated BMI was associated with reduced mortality in patients with AF. This association was modified by DM. The obesity paradox confined to AF patients without DM, but could not be generalized to those with DM.     

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement

BackgroundMyocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood.ObjectivesThe purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR).MethodsThis retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction–confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR.ResultsIn this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003).ConclusionsIn this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.