A novel prognostic tool to predict mortality in patients with atrial fibrillation: The BASIC-AF risk score

BackgroundThis study sought to develop and validate a risk score to predict mortality in patients with atrial fibrillation (AF) after a hospitalization for cardiac reasons.MethodsThe new risk score was derived from a prospective cohort of hospitalized patients with concurrent AF. The outcome measures were all-cause and cardiovascular mortality. Random forest was used for variable selection. A risk points model with predictor variables was developed by weighted Cox regression coefficients and was internally validated by bootstrapping.ResultsIn total, 1130 patients with AF were included. During a median follow-up of 2 years, 346 (30.6%) patients died and 250 patients had a cardiovascular cause of death. N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T were the most important predictors of mortality, followed by indexed left atrial volume, history and type of heart failure, age, history of diabetes mellitus, and intraventricular conduction delay, all forming the BASIC-AF risk score (Biomarkers, Age, ultraSound, Intraventricular conduction delay, and Clinical history). The score had good discrimination for all-cause (c-index = 0.85 and 95% CI 0.82–0.88) and cardiovascular death (c-index = 0.84 and 95% CI 0.81-0.87). The predicted probability of mortality varied more than 50-fold across deciles and adjusted well to observed mortality rates. A decision curve analysis revealed a significant net benefit of using the BASIC-AF risk score to predict the risk of death, when compared with other existing risk schemes.ConclusionsWe developed and internally validated a well-performing novel risk score for predicting death in patients with AF. The BASIC-AF risk score included routinely assessed parameters, selected through machine-learning algorithms, and may assist in tailored risk stratification and management of these patients.     

Machine Learning Identifies Clinical Parameters to Predict Mortality in Patients Undergoing Transcatheter Mitral Valve Repair

ObjectivesThe aim of this study was to develop a machine learning (ML)–based risk stratification tool for 1-year mortality in transcatheter mitral valve repair (TMVR) patients incorporating metabolic and hemodynamic parameters.BackgroundThe lack of appropriate, well-validated, and specific means to risk-stratify patients with mitral regurgitation complicates the evaluation of prognostic benefits of TMVR in clinical trials and practice.MethodsA total of 1,009 TMVR patients from 3 university hospitals within the Heart Failure Network Rhineland were included; 1 hospital (n = 317) served as external validation. The primary endpoint was all-cause 1-year mortality. Model performance was assessed using receiver-operating characteristic curve analysis. In the derivation cohort, different ML algorithms were tested using 5-fold cross-validation. The final model, called MITRALITY (transcatheter mitral valve repair mortality prediction system) was tested in the validation cohort with respect to existing clinical scores.ResultsExtreme gradient boosting was selected for the MITRALITY score, using only 6 baseline clinical features for prediction (in order of predictive importance): urea, hemoglobin, N-terminal pro–brain natriuretic peptide, mean arterial pressure, body mass index, and creatinine. In the external validation cohort, the MITRALITY score’s area under the curve was 0.783 (95% CI: 0.716-0.849), while existing scores yielded areas under the curve of 0.721 (95% CI: 0.63-0.811) and 0.657 (95% CI: 0.536-0.778) at best.ConclusionsThe MITRALITY score is a novel, internally and externally validated ML-based tool for risk stratification of patients prior to TMVR, potentially serving future clinical trials and daily clinical practice.     

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)     

A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction

ObjectivesThis study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure.BackgroundA cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI).MethodsThe Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score.ResultsThere were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score.ConclusionsThis noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850)     

Dose–response relationship between distinct serum uric acid trajectories and metabolic syndrome risk: A 5-year prospective cohort study

Background and aimsAlthough high serum uric acid (SUA) at baseline has been linked to increased risk for metabolic syndrome (MetS), the association of longitudinal SUA changes with MetS risk is unclear. We aimed to examine the effect of distinct SUA trajectories on new-onset MetS risk by sex in a Chinese cohort.Methods and resultsA total of 2364 women and 2770 men who were free of MetS in 2013 were enrolled in this study and followed up to 2018. Group-based trajectory modeling was applied to identify SUA trajectories. Cox proportional hazards model was used to evaluate the association between SUA trajectory and new-onset MetS. The dose–response relationship between SUA trajectories and MetS risk was examined by treating trajectory groups as a continuous variable. During a median follow-up of 48.0 months, 311 (13.16%) women and 950 (34.30%) men developed MetS. SUA trajectories (2013–2018) were defined as four distinct patterns in both women and men: “low”, “moderate”, “moderate-high”, and “high”. Compared with “low” SUA trajectory, the adjusted hazard ratio for incident MetS among participants with “moderate”, “moderate-high” and “high” trajectory was in a dose–response manner: 1.75 (95% CI: 1.08–2.82), 1.94 (95% CI: 1.20–3.14), and 3.05 (95% CI: 1.81–5.13), respectively, for women; 1.20 (95% CI: 0.97–1.49), 1.48 (95% CI: 1.19–1.85), and 1.66 (95% CI: 1.25–2.21), respectively, for men.ConclusionsElevated SUA trajectories are associated with increased risk for new-onset MetS in women and men. Monitoring SUA trajectories may assist in identifying subpopulations at higher risk for MetS.     

The association between meat intake and the risk of coronary heart disease in Korean men using the Framingham risk score: A prospective cohort study

Background and aimsResearch suggests that meat intake may increase the risk of coronary heart disease (CHD), but most studies take place in Western countries, where the types and amount of meat products consumed differ from those in Asian countries. We aimed to identify the association between meat intake and CHD risk in Korean male adults, using the Framingham risk score.Methods and resultsWe used data from the Korean Genome and Epidemiology Study (KoGES) Health Examinees (HEXA) study, including 13,293 Korean male adults. We estimated the association of meat intake with ≥20% 10-year CHD risk using Cox proportional hazards regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects with the highest total meat intake had a 53% (model 4: HR 1.53, 95% CI 1.05–2.21) increased 10-year CHD risk compared to those with the lowest intake. Those with the highest red meat intake had a 55% (model 3: HR 1.55, 95% CI 1.16–2.06) increased 10-year CHD risk compared to those with the lowest intake. No association was observed between poultry or processed meat intake and 10-year CHD risk.ConclusionsConsumption of total meat and red meat was associated with a higher risk of CHD in Korean male adults. Further studies are needed to provide criteria for the appropriate meat intake by meat type to reduce CHD risk.     

A Clinical Tool to Identify Candidates for Stress-First Myocardial Perfusion Imaging

ObjectivesThis study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients.BackgroundThere is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience.MethodsA secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028).ResultsFinal models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively.ConclusionsA novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols.     

Carbohydrate intake and risk of metabolic syndrome: A dose–response meta-analysis of observational studies

Background and aimsEpidemiological association studies have reported inconsistent findings on the relationship between carbohydrate intake and risk of metabolic syndrome (MetS). Therefore, we aimed to conduct the first dose–response meta-analysis to investigate this effect.Methods and resultsA systematic search in PubMed and Web of Science databases from their inception to June 01, 2019, together with relevant literature scrutiny, was performed to identify related studies for inclusion into the meta-analysis. We calculated the odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Furthermore, subgroup, sensitivity, heterogeneity, and publication bias analyses were performed. This meta-analysis included 14 cross-sectional and four cohort studies, totaling 284,638 participants and 69,554 MetS cases. The highest versus the lowest carbohydrate intake values were associated with an increased risk of MetS (OR: 1.253, 95% CI: 1.147–1.368), with moderate heterogeneity (I² = 54.5%). Using dose–response analysis, we found a linear association between carbohydrate consumption and MetS risk with a corresponding OR of 1.026 (95% CI, 1.004–1.048) and with significant heterogeneity (I² = 82.0%) at 5% energy intake from carbohydrates. We have found similar results using subgroup analyses for major study characteristics and adjustment for confounders. Sensitivity analysis further enhanced the robustness of the results, and no publication bias was detected.ConclusionCarbohydrate intake is associated with an increased risk of developing MetS. Therefore, additional large prospective cohort studies are warranted to confirm our findings.     

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.     

The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia

ObjectivesThis study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).BackgroundCommon cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).MethodsREFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.ResultsWe included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.ConclusionsCAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.     

Association of Life's Essential 8 with all-cause and cardiovascular mortality among US adults: A prospective cohort study from the NHANES 2005–2014

Background and aimsThis study aims to investigate the association of Life's Essential 8 (LE8), the recently updated algorithm for quantifying cardiovascular health (CVH) by the American Heart Association (AHA), with long-term outcomes among US adults.Methods and resultsThis population-based prospective cohort study analyzed data of 23,110 participants aged 20 years or older from the National Health and Nutrition Examination Survey from 2005 to 2014 and their linked mortality data through December 2019. LE8 score (range 0–100) was measured according to AHA definitions and was categorized into low (0–49), moderate (50–79), and high (80–100) CVH. The weighted mean age of the study population was 47.0 years (95% confidence interval [CI], 46.4–47.5 years), and 11,840 were female (weighted percentage, 51.5%; 95% CI, 50.9–52.1%). During a median follow-up period of 113 months (up to 180 months), 2942 all-cause deaths occurred, including 738 CVD deaths. The LE8 score was significantly and inversely related to mortality from all causes (adjusted hazard ratio [HR] for per 10-score increase in LE8 score, 0.86; 95% CI, 0.82–0.90) and cardiovascular disease (adjusted HR for per 10-score increase in LE8 score, 0.81; 95% CI, 0.75–0.87). Compared with participants having low CVH, those having high CVH had a reduction of 40% (adjusted HR, 0.60; 95% CI, 0.48–0.75) in the risk for all-cause mortality and 54% (adjusted HR, 0.46; 95% CI, 0.31–0.68) in the risk for cardiovascular mortality.ConclusionsHigher LE8 score was independently associated with lower risks of all-cause and cardiovascular mortality among US adults.     

Performance of stent thrombosis and bleeding risk scores in out-of-hospital cardiac arrest due to acute coronary syndromes

BackgroundPatients with out-of-hospital cardiac arrest (OHCA) due to acute coronary syndromes (ACS) who undergo percutaneous coronary intervention (PCI) are at high risk of bleeding and thrombosis. While predictive bleeding and stent thrombosis risk scores have been established, their performance in patients with OHCA has not been evaluated.MethodsAll consecutive patients admitted for OHCA due to ACS who underwent PCI between January 2007 and December 2019 were included. The ACTION and CRUSADE bleeding risk scores and the Dangas score for early stent thrombosis risk were calculated for each patient. A C-statistic analysis was performed to assess the performance of these scores.ResultsAmong 386 included patients, 82 patients (21.2%) experienced severe bleeding and 30 patients (7.8%) experienced stent thrombosis. The predictive performance of the ACTION and CRUSADE bleeding risk scores for major bleeding was poor, with areas under the curve (AUCs) of 0.596 and 0.548, respectively. Likewise, the predictive performance of the Dangas stent thrombosis risk score was poor (AUC 0.513). Using multivariable analysis, prolonged low-flow (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05; P = 0.025), reduced haematocrit or fibrinogen at admission (OR 0.93, 95% CI 0.88–0.98; P = 0.010 and OR 0.61; 95% CI 0.41–0.89; P = 0.012, respectively) and the use of glycoprotein IIb/IIIa inhibitors (OR 2.10, 95% CI 1.18–3.73; P = 0.011) were independent risk factors for major bleeding.ConclusionThe classic bleeding and stent thrombosis risk scores have poor performance in a population of patients with ACS complicated by OHCA. Other predictive factors might be more pertinent to determine major bleeding and stent thrombosis risks in this specific population.     

Interplay of Coronary Artery Calcium and Risk Factors for Predicting CVD/CHD Mortality: The CAC Consortium

ObjectivesThis study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk.BackgroundAlthough CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate.MethodsThe CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD.ResultsDuring the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0.ConclusionsAcross the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.     

Pancreatic exocrine insufficiency is a risk factor for kidney stones in patients with chronic pancreatitis

IntroductionMost patients with chronic pancreatitis (CP) develop pancreatic exocrine insufficiency (PEI) over the course of the disease. PEI may lead to hyperoxaluria and development of urinary oxalate stones. It has been postulated that the patients with CP may be at increased risk of kidney stone formation, but the data is scarce. We aimed to estimate incidence and risk factors for nephrolithiasis in a Swedish cohort of patients with CP.Patients and methodsWe performed retrospective analysis of an electronical medical database of patients diagnosed with definite CP during 2003–2020. We excluded patients <18 years of age, those with missing relevant data in medical charts, patients with probable CP (according to the M-ANNHEIM classification system) and those in whom kidney stones were diagnosed before CP diagnosis.ResultsSome 632 patients with definite CP were followed over a median of 5.3 (IQR 2.4–6.9) years. There were 41 (6.5%) patients diagnosed with kidney stones, of whom 33 (80.5%) were symptomatic. Comparing to patients without kidney stones, patients with nephrolithiasis were older, with median age of 65 (IQR 51–72) years, and a male predominance (80% vs 63%). Cumulative incidence of kidney stones was 2.1%, 5.7%, 12.4% and 16.1% at 5, 10, 15, and 20 years after CP diagnosis, respectively. Multivariable cause-specific Cox regression analysis revealed PEI as independent risk factor for nephrolithiasis (adjusted HR 4.95, 95%CI 1.65–14.84; p = 0.004). Another risk factors were increase in BMI (aHR 1.16 95% CI 1.04–1.30; p = 0.001 per unit increment), and a male sex (4.51, 95% CI 1.01–20.3, p = 0.049).ConclusionPEI and increase in BMI are risk factors for kidney stone development in patients with CP. Male CP patents are particularly at increased risk of nephrolithiasis. This should be taken into consideration in general clinical approach to raise awareness among patients and medical workers.     

Triglycerides and Residual Atherosclerotic Risk

BackgroundEven when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.ObjectivesThis study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.MethodsAn observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.ResultsAtherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003).ConclusionsIn individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)     

Association between dietary fiber intake and risk of incident aortic stenosis

Background and aimsAlthough aortic stenosis is the most common valvular heart disease requiring intervention in Europe, the role that diet plays in development of the disease is largely unknown. The pathophysiology of aortic stenosis is however similar to other cardiovascular diseases that fiber intake has been associated with. The aim of this study was consequently to investigate the association between dietary fiber intake as well as the main food sources of fiber, i.e. fruit and vegetables and whole grains, and risk of incident aortic stenosis.Methods and resultsThe Malmö Diet and Cancer Study is a Swedish prospective population-based cohort study with baseline data collection performed between year 1991–1996. Dietary habits were recorded through seven-day food diaries, 168-item diet questionnaires, and interviews, and data on incident aortic stenosis was collected through national registers. Among the 26,063 participants, 672 cases were ascertained during a mean follow-up period of 20 years. Cox regression was used to estimate the association between dietary intakes and incident aortic stenosis. No associations were found between incident aortic stenosis and intake of dietary fiber (HR for the highest vs lowest quintile: 0.93; 95% CI: 0.72–1.24), fruit and vegetables (HR: 0.98; 95% CI: 0.76–1.28), or whole grains (HR: 1.00; 95% CI: 0.79–1.26) in the main model.ConclusionThe findings of this study do not indicate that consumption of dietary fiber or fiber rich foods are associated with incident aortic stenosis.     

Derivation,Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel: The ABCD-GENE Score

ObjectivesThe aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes.BackgroundClopidogrel is the most broadly used platelet P2Y₁₂ inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects. Although carriers of loss-of-function alleles of the cytochrome P450 2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of HPR and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles.MethodsThree prospective and independent studies were used to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel; 2) investigate the external validity of the risk score; and 3) define clinical outcomes associated with the risk score in a cohort of patients with myocardial infarction treated with clopidogrel.ResultsA risk score ABCD-GENE (Age, Body Mass Index, Chronic Kidney Disease, Diabetes Mellitus, and Genotyping) was developed incorporating 5 independent predictors of HPR: 4 clinical (age >75 years, body mass index >30 kg/m², chronic kidney disease [glomerular filtration rate <60 ml/min], and diabetes mellitus) and 1 genetic (cytochrome P450 2C19 loss-of-function alleles). The C-statistics for the score as an integer variable were 0.71 (95% confidence interval [CI]: 0.68 to 0.75) and 0.64 (95% CI: 0.60 to 0.67) in the pharmacodynamic derivation and validation cohorts, respectively. A cutoff score ≥10 was associated with the best sensitivity and specificity to identify HPR status. The C-statistics for the score were 0.67 (95% CI: 0.64 to 0.71) for all-cause death and 0.66 (95% CI: 0.63 to 0.69) for the composite of all-cause death, stroke, or myocardial infarction at 1 year. Using multiple models for adjustment, the ABCD-GENE score consistently and independently correlated with all-cause death, as well as with the composite of all-cause death, stroke, or myocardial infarction, both as a continuous variable and by using the cutoff of ≥10. The score did not predict bleeding.ConclusionsThe ABCD-GENE score is a simple tool to identify patients with HPR on clopidogrel and who are at increased risk for adverse ischemic events, including mortality, following an acute myocardial infarction. In patients with a high ABCD-GENE score, long-term oral P2Y₁₂ inhibitors other than clopidogrel should be considered.     

Resuscitation Using ECPR During In-Hospital Cardiac Arrest (RESCUE-IHCA) Mortality Prediction Score and External Validation

ObjectivesThe aim of this study was to develop and validate a score to accurately predict the probability of death for adult extracorporeal cardiopulmonary resuscitation (ECPR).BackgroundECPR is being increasingly used to treat refractory in-hospital cardiac arrest (IHCA), but survival varies from 20% to 40%.MethodsAdult patients with extracorporeal membrane oxygenation for IHCA (ECPR) were identified from the American Heart Association GWTG-R (Get With the Guidelines–Resuscitation) registry. A multivariate survival prediction model and score were developed to predict hospital death. Findings were externally validated in a separate cohort of patients from the Extracorporeal Life Support Organization registry who underwent ECPR for IHCA.ResultsA total of 1,075 patients treated with ECPR were included. Twenty-eight percent survived to discharge in both the derivation and validation cohorts. A total of 6 variables were associated with in-hospital death: age, time of day, initial rhythm, history of renal insufficiency, patient type (cardiac vs noncardiac and medical vs surgical), and duration of the cardiac arrest event, which were combined into the RESCUE-IHCA (Resuscitation Using ECPR During IHCA) score. The model had good discrimination (area under the curve: 0.719; 95% CI: 0.680-0.757) and acceptable calibration (Hosmer and Lemeshow goodness of fit P = 0.079). Discrimination was fair in the external validation cohort (area under the curve: 0.676; 95% CI: 0.606-0.746) with good calibration (P = 0.66), demonstrating the model’s ability to predict in-hospital death across a wide range of probabilities.ConclusionsThe RESCUE-IHCA score can be used by clinicians in real time to predict in-hospital death among patients with IHCA who are treated with ECPR.     

Comparative Risk of Angioedema With Sacubitril-Valsartan vs Renin-Angiotensin-Aldosterone Inhibitors

BackgroundData on angioedema risk among sacubitril-valsartan (SV) users in real-world settings are limited.ObjectivesWe sought to evaluate the risk of angioedema among SV new users compared with angiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor-blocker (ARB) new users separately.MethodsWe conducted a propensity score–matched cohort study, comparing SV new users (no use of SV, ACE inhibitor, ARB 6 months before) and SV new users with prior use (within 183 or 14 days) of ACE inhibitor or ARB (ACE inhibitor–SV and ARB-SV users; recent ACE inhibitor–SV and recent ARB-SV users, respectively) vs ACE inhibitor and ARB new users separately.ResultsCompared with ACE inhibitor, SV new (HR: 0.18; 95% CI: 0.11-0.29) and ACE inhibitor–SV users (HR: 0.31; 95% CI: 0.23-0.43) showed lower risk of angioedema. On the other hand, there was no difference in angioedema risk when SV new users (HR: 0.59; 95% CI: 0.35-1.01) or ARB-SV users (HR: 0.85; 95% CI: 0.58-1.26) were compared with ARB new users. Compared with SV new users, ACE inhibitor–SV users (HR: 1.62; 95% CI: 0.91-2.89) trended toward higher angioedema risk, which intensified when the ACE inhibitor to SV switch occurred within 14 days (recent ACE inhibitor–SV) (HR: 1.98; 95% CI: 1.11-3.53). Similarly, ARB-SV users (HR: 2.03; 95% CI: 1.16-3.54) experienced an increased risk compared with SV new users, which intensified for the more recent switchers (recent ARB-SV) (HR: 2.45; 95% CI: 1.36-4.43).ConclusionsWe did not observe an increased risk of angioedema among SV new users compared with ACE inhibitor or ARB users. However, there was an increased risk of angioedema among SV users who recently switched from ACE inhibitor or ARB compared with SV new users.     

Association between the visceral adiposity index and risks of all-cause and cause-specific mortalities in a large cohort: Findings from the UK biobank

Background and aimsThe visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined.Methods and resultsIn this large-scale prospective epidemiological study, 357,457 participants (aged 38–73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148–1.255; P < 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150–1.303; P < 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148–1.255; P < 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148–1.255; P < 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25.ConclusionIn summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.