Incidence Of Cardiovascular Events In Patients Research Articles

Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis.

The current umbrella review aimed to evaluate the effect of metformin on all-cause mortality (ACM), cardiovascular mortality, and cardiovascular disease (CVD) incidence in DM patients. PubMed, Scopus, Cochrane, Google Scholar, and Web of Science databases were searched with special keywords. Related studies were included after screening by two independent investigators based on title and full texts. The AMSTAR2 checklist was used to assess the quality of studies, and Cochran tests were used to assess the heterogeneity between studies. Overall, seventeen systematic reviews and meta-analysis studies were included. The results revealed that the risk of ACM in patients who received metformin was lower than in patients who did not receive metformin. (OR: 0.80, 95% CI:0.744,0.855); also, the risk of CVD mortality in metformin patients was lower than in the other two groups (placebo and other anti-diabetic drugs) (OR: 0.771, 95% CI:0.688,0.853, P:0.001). The risk of CVD in metformin users was also lower than in the other two groups (OR: 0.828, 95% CI:0.781,0.785). This comprehensive review showed that the risk of ACM, death due to CVD, and incidents of CVD in DM who use metformin was lower than the patients who received a placebo only or other diabetic drugs, which can guide clinicians in medical decision-making. The online version contains supplementary material available at 10.1007/s40200-023-01309-y.

ANGPTL3 and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea.

Background The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5]ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA. Conclusions In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.

Prevalence and prognosis of molecularly defined familial hypercholesterolemia in patients with acute coronary syndrome.

BackgroundFamilial hypercholesterolemia (FH) can elevate serum low-density lipoprotein cholesterol (LDL-C) levels, which can promote the progression of acute coronary syndrome (ACS). However, the effect of FH on the prognosis of ACS remains unclear.MethodsIn this prospective cohort study, 223 patients with ACS having LDL-C ≥ 135.3 mg/dL (3.5 mmol/L) were enrolled and screened for FH using a multiple-gene FH panel. The diagnosis of FH was defined according to the ACMG/AMP criteria as carrying pathogenic or likely pathogenic variants. The clinical features of FH and the relationship of FH to the average 16.6-month risk of cardiovascular events (CVEs) were assessed.ResultsThe prevalence of molecularly defined FH in enrolled patients was 26.9%, and coronary artery lesions were more severe in patients with FH than in those without (Gensini score 66.0 vs. 28.0, respectively; P < 0.001). After lipid lowering, patients with FH still had significantly higher LDL-C levels at their last visit (73.5 ± 25.9 mg/dL vs. 84.7 ± 37.1 mg/dL; P = 0.013) compared with those without. FH increased the incidence of CVEs in patients with ACS [hazard ratio (HR): 3.058; 95% confidence interval (CI): 1.585–5.900; log-rank P < 0.001].ConclusionFH is associated with an increased risk of CVEs in ACS and is an independent risk factor for ACS. This study highlights the importance of genetic testing of FH-related gene mutations in patients with ACS.

Abstract 9341: Hepatic Steatosis Index and Fibrosis-4 Scores in Patients With Type 2 Diabetes - Post Hoc Analyses from VERTIS CV

Introduction: Given the potential link between non-alcoholic fatty liver disease and increased cardiovascular (CV) risk, the associations between markers of hepatic steatosis/fibrosis with CV and kidney outcomes were explored. Methods: These post hoc analyses were conducted on data from the VERTIS CV trial that randomized patients with type 2 diabetes (T2D) and atherosclerotic CV disease (ASCVD) to ertugliflozin 5 or 15 mg or placebo, with all randomized groups pooled for the present analyses. The presence of hepatic steatosis was estimated by hepatic steatosis index (HSI; 8 х ALT/AST + BMI + 2 if T2D + 2 if female); and for hepatic fibrosis, fibrosis-4 score (FIB-4; [age х AST]/[platelets count х √ALT]). Patients were divided into quartiles (Q1 to Q4) according to baseline for each score. CV and kidney outcomes (CV death/myocardial infarction/stroke [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and sustained ≥40% decrease in eGFR from baseline/dialysis or transplantation/kidney death) were stratified by baseline HSI and FIB-4 quartiles. Results: Among 8246 patients, the mean age was 64.4 years, mean BMI 32.0 kg/m 2 , mean HSI 44.0, and mean FIB-4 score 1.34. Event rates of MACE, HHF/CV death, CV death, and HHF increased with FIB-4 quartile ( Fig A ). The hazard ratios (HR, 95% CI) of events by FIB-4 quartile (Q4 vs Q1) were 1.48 (1.25, 1.76), 2.0 (1.63, 2.51), 1.85 (1.45, 2.36), and 2.94 (1.98, 4.37) for MACE, HHF/CV death, CV death, and HHF, respectively. The kidney composite did not differ across FIB-4 quartiles. CV and kidney outcomes did not differ across HSI quartiles, except for higher incidence of HHF in the upper HSI quartile (HR [95% CI], Q4 vs Q1: 1.52 [1.07, 2.17]) ( Fig B ). Conclusion: In VERTIS CV, baseline fibrosis scores were associated with incident CV events in patients with T2D and ASCVD, despite the upper cutoff excluding advanced fibrosis. Steatosis only correlated with HHF, and neither measure was associated with the composite kidney outcome.

Higher levels of anti-phosphorylcholine autoantibodies in early rheumatoid arthritis indicate lower risk of incident cardiovascular events

BackgroundThe increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. It has been suggested that anti-phosphorylcholine antibodies (anti-PC) of the IgM subclass may have atheroprotective effects. Here, we aimed to investigate the association between levels of IgM anti-PC antibodies with CVE in patients with early RA.MethodsThe study population was derived from the BARFOT early RA cohort, recruited in 1994–1999. The outcome of incident CVE (AMI, angina pectoris, coronary intervention, ischemic stroke, TIA) was tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM. The Kaplan-Meier estimates and Cox proportional hazards regression models were used to compare CV outcome in the groups categorized by baseline median level of IgM anti-PC.ResultsIn all, 653 patients with early RA, 68% women, mean (SD) age 54.8 (14.7) years, DAS28 5.2 (1.3), 68% seropositive, and without prevalent CVD, were included. During the follow-up of mean 11.7 years, 141 incident CVE were recorded.Baseline IgM anti-PC above median was associated with a reduction in risk of incident CVE in patients aged below 55 years at inclusion, HR 0.360 (95% CI, 0.142–0.916); in males, HR 0.558 (0.325–0.958); in patients with BMI above 30 kg/m2, HR 0.235 (0.065–0.842); and in those who did not achieve DAS28 remission at 1 year, HR 0.592 (0.379–0.924). The pattern of associations was confirmed in the models with AUC IgM anti-PC over 2 years.ConclusionProtective effects of higher levels of innate IgM anti-PC autoantibodies on CVE were detected in younger patients with RA and those at high risk of CVE: males, presence of obesity, and non-remission at 1 year.

Low bone mineral density is associated with coronary arterial calcification progression and incident cardiovascular events in patients with chronic kidney disease.

ABSTRACTBackgroundAlthough it is well known that low bone mineral density (BMD) is associated with an increased risk of cardiovascular disease (CVD) and mortality in the general population, the prognostic role of bone mineral density (BMD) has not been established in the chronic kidney disease (CKD) population. Therefore we aimed to evaluate the association between BMD and the risk of CVD and cardiovascular mortality in patients with predialysis CKD.MethodsThis prospective cohort study was conducted with 1957 patients with predialysis CKD Stages 1–5. BMD was measured using dual-energy X-ray absorptiometry and coronary arterial calcification (CAC) scores were evaluated using coronary computed tomography. The primary outcome was a major adverse cardiovascular event (MACE).ResultsWhen patients were classified based on total hip BMD T-score tertiles stratified by sex, the lowest BMD tertile was significantly associated with an increased risk of MACE {hazard ratio 2.16 [95% confidence interval (CI) 1.25–3.74]; P = 0.006}. This association was also shown with BMD at the femur neck but not with BMD at lumbar spine. In the subgroup of 977 patients with follow-up CACs at their fourth year, 97 (9.9%) showed accelerated CAC progression (>50/year), and BMD was inversely associated with accelerated CAC progression even after adjusting for the baseline CAC score [odds ratio 0.75 (95% CI 0.58–0.99); P = 0.039]. In addition, baseline CAC was associated with an increased risk of MACEs after adjusting for total hip T-score.ConclusionsLow BMD was significantly associated with CAC progression and MACEs in patients with predialysis CKD.

Targeted metabolomic profiling and prediction of cardiovascular events: a prospective study of patients with psoriatic arthritis and psoriasis

ObjectiveIn patients with psoriatic disease (PsD), we sought serum metabolites associated with cardiovascular (CV) events and investigated whether they could improve CV risk prediction beyond traditional risk factors and the...

Urine High-Sensitivity Troponin I Predict Incident Cardiovascular Events in Patients with Diabetes Mellitus.

In patients with diabetes mellitus (DM), incident cardiovascular (CV) events are associated with poor long-term outcomes. Serum high-sensitivity troponin I (hs-TnI) is widely used to diagnose and predict outcomes in patients with acute coronary syndrome, however, few studies have investigated the accuracy of urine hs-TnI as a predictor for incident CV events in patients with DM. The enrolled participants included patients with DM. Fresh urine hs-TnI levels were measured. Medical records of enrolled patients were used to determine the number of incident CV events prospectively for 3 months. The study cohort comprised 378 participants. We observed significantly higher levels of urine hs-TnI in those with than without subsequent incident CV events. The multivariate logistic regression analysis using different models consistently showed that urine hs-TnI > 4.10 pg/mL was an independent factor predictive of incident CV events. The ROC-AUC analysis revealed that the optimal cutoff value for urine hs-TnI for predicting incident CV events was 1.55 pg/mL and the area was 0.611 (p = 0.027). A single measurement of urinary hs-TnI, collected easily and non-invasively, may be an acceptable biomarker for predicting subsequent incident CV events in patients with DM.

Risk of cardiovascular events in patients with atrial fibrillation and cancer. Data from the ATHERO-AF cohort

Abstract Background Patients with non valvular atrial fibrillation (AF) and cancer represent a high-risk subgroup of patients in whom the management of oral anticoagulation may be challenging. The relationship between cancer type and the risk of cardiovascular events (CVEs) in patients with AF is unclear. Purpose To investigate the incidence of CVEs in patients with AF and cancer according to cancer type. Methods Prospective cohort study including 2,092 consecutive AF patients on vitamin K antagonists. Principal endpoint was the occurrence of CVEs including fatal/non-fatal myocardial infarction and ischemic stroke and cardiovascular death. We also performed a subgroup analysis of cardiac and thromboembolic events separately. Patients with cancer were divided in subgroups based on cancer site as follows: group 1 gastrointestinal tract; group 2 respiratory tract; group 3 genitourinary tract; group 4 other sites. Results Mean age was 73.7±9.1 years and 42.1% were woman; 367 (17.5%) had cancer, of these 21% gastro-intestinal, 10% respiratory, 28% genito-urinary and 41% had other localization. Patients with cancer were older than those without but with similar clinical characteristics. During a mean follow up of 35.9±28.0 months (6264.5 patient-years), 203 CVEs occurred (3.24%/year, 95% CI 2.81–3.72) of whom 86 were cardiac ischemia (1.37%/year, 95% CI 1.10–1.69), 70 thromboembolic events (1.12%/year, 95% CI 0.87–1.41) and 47 cardiovascular deaths (0.75%/year, 95% CI 0.55–0.99). The incidence of CVEs for AF patients with and without cancer was respectively (n=45, 3.78%, 95% CI 2.76–5.06) and (n=158, 3.11%/year, 95% CI 2.65–3.64). In particular, compared to patients without cancer, a higher incidence rate of CVEs was found in patients with gastrointestinal tract cancer (5.61%/year, 95% CI 2.90–9.79, p=0.046), and in patients with respiratory tract cancer (6.15%/year, 95% CI 2.66–12.1, p=0.055), while no difference was found in patients with genito-urinary tract cancer (2.24%/year, 95% CI 0.97–4.41, p=0.362) and other site cancer (3.11%/year, 95% CI 2.65–3.64, p=0.512). Cox regression multivariate analysis showed that factors associated with cardiac events were COPD, dyslipidemia, TTR &amp;lt;70%, PPI drugs and gastrointestinal cancer (figure). Conversely, CHA2DS2VASc score and respiratory cancer were predictors of thromboembolic events. Conclusions Our findings suggest an association between cancer type and specific ischemic complications in AF patients. In particular, we found a higher risk of cardiac complications in patients with gastrointestinal cancer and of thromboembolic events in patients with respiratory cancer. These associations need to be confirmed in larger studies. Funding Acknowledgement Type of funding source: None

Anti-Citrullinated Protein Antibody Specificities, Rheumatoid Factor Isotypes, and Incident Cardiovascular Events in Patients With Rheumatoid Arthritis.

To investigate the relationship between anti-citrullinated protein antibodies (ACPAs), specific ACPA subspecificities, rheumatoid factor (RF) isotypes, and incident cardiovascular (CV) events in patients with rheumatoid arthritis (RA). Serum samples from Swedish patients with new-onset RA (diagnosed within 1 year of symptom onset between 1996 and 2009) were centrally typed for anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies, 20 ACPA subspecificities, and RF isotypes. Patients were followed up longitudinally in nationwide registers to monitor the occurrence of acute coronary syndrome (ACS), stroke, CV-related death, and major adverse CV events (MACE). The association between each serologic marker and CV outcome, and the impact of adjustment for the Disease Activity Score in 28 joints (DAS28), smoking status, and income at baseline, were assessed using Cox proportional hazards models. In addition, associations of serologic markers with all-cause mortality were explored. In total, 2,814 patients with RA were included in the study. The median follow-up was 13 years, during which the CV end points of ACS, stroke, or CV-related death were reported to occur in 375 patients. Occurrence and/or levels of anti-CCP2 were associated with risk of incident ACS (hazard ratio [HR] 1.46, 95% confidence interval [95% CI] 1.03-2.06), stroke (HR 1.47, 95% CI 1.03-2.10), CV-related death (P = 0.024 for association with anti-CCP2 levels), and MACE (HR 1.34, 95% CI 1.06-1.70). Similarly, an association with the number of ACPA subspecificities was observed; however, this could not be attributed to any individual or group of ACPA subspecificities. Presence of IgM-RF was associated with all CV end points except ACS, and IgA-RF was exclusively associated with CV-related death. Adjustment for smoking status, income, and DAS28 scores decreased most of the HRs, whereas IgA-RF remained associated with CV-related death (HR 1.61, 95% CI 1.05-2.48). All of the assessed serologic makers were associated with all-cause mortality. RF isotypes and ACPAs are associated with future CV events in patients with RA. ACPA levels and number of subspecificities seem more important than the occurrence of particular subspecificities, and these associations were not explained by a history of ever smoking.

Application of a machine learning-driven, multibiomarker panel for prediction of incident cardiovascular events in patients with suspected myocardial infarction.

Background: In patients with suspected myocardial infarction (MI), we sought to validate a machine learning-driven, multibiomarker panel for prediction of incident major adverse cardiovascular events (MACE). Methodology & results: A previously described prognostic panel for MACE consisting of four biomarkers was measured in 748 patients with suspected MI. The investigated end point was incident MACE within 1 year. The prognostic value of a continuous score and an optimal cut-off was investigated. The area under the curve was 0.86 for the overall model. Using the optimal cut-off resulted in a negative predictive value of 99.4% for incident MACE. Patients with an elevated prognostic score were at high risk for MACE. Conclusion: Among patients with suspected MI, we validated a multibiomarker panel for predicting 1-year MACE. Clinical Trial Registration: NCT02355457 (ClinicalTrials.gov).

Value of Carotid Ultrasound in Cardiovascular Risk Stratification in Patients With Psoriatic Disease.

This study aimed to assess whether subclinical atherosclerosis, as evaluated by carotid ultrasound, could predict incident cardiovascular events (CVEs) in patients with psoriatic disease (PsD) and determine whether incorporation of imaging data could improve CV risk prediction by the Framingham Risk Score (FRS). In this cohort analysis, patients with PsD underwent ultrasound assessment of the carotid arteries at baseline. The extent of atherosclerosis was assessed using carotid intima-media thickness (CIMT) and total plaque area (TPA). Incident CVEs (new or recurrent) that occurred following the ultrasound assessment were identified. The association between measures of carotid atherosclerosis and the risk of developing an incident CVE was evaluated using Cox proportional hazards models, with adjustment for the FRS. In total, 559 patients with PsD were assessed, of whom 23 had incident CVEs ascertained. The calculated rate of developing a first CVE during the study period was 1.11 events per 100 patient-years (95% confidence interval [95% CI] 0.74-1.67). When analyzed separately in Cox proportional hazards models that were controlled for the FRS, the TPA (hazard ratio [HR] 3.74, 95% CI 1.55-8.85; P = 0.003), mean CIMT (HR 1.21, 95% CI 1.03-1.42; P = 0.02), maximal CIMT (HR 1.11, 95% CI 1.01-1.22; P = 0.03), and high TPA category (HR 3.25, 95% CI 1.18-8.95; P = 0.02) were each predictive of incident CVEs in patients with PsD. The burden of carotid atherosclerosis is associated with an increased risk of developing future CVEs. Combining vascular imaging data with information on traditional CV risk factors could improve the accuracy of CV risk stratification in patients with PsD.

Trimethyllysine, a trimethylamine N-oxide precursor, provides near- and long-term prognostic value in patients presenting with acute coronary syndromes.

Trimethyllysine (TML) serves as a nutrient precursor of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) and is associated with incident cardiovascular (CV) events in stable subjects. We examined the relationship between plasma TML levels and incident CV events in patients presenting with acute coronary syndromes (ACS). Plasma levels of TML were quantified in two independent cohorts using mass spectrometry, and its relationship with CV events was investigated. In a Cleveland Cohort (N = 530), comprised of patients presenting to the emergency department with chest pain and suspected ACS, TML was associated with major adverse cardiac events (MACE, myocardial infarction, stroke, need for revascularization, or all-cause mortality) over both 30 days [3rd tertile (T3), adjusted odds ratio (OR) 1.77, 95% confidence interval (CI) 1.04-3.01; P < 0.05] and 6 months (T3, adjusted OR 1.95, 95% CI 1.15-3.32; P < 0.05) of follow-up independent of traditional CV risk factors and indices of renal function. Elevated TML levels were also associated with incident long-term (7-year) all-cause mortality [T3, adjusted hazard ratio (HR) 2.52, 95% CI 1.50-4.24; P < 0.001], and MACE even amongst patients persistently negative for cardiac Troponin T at presentation (e.g. 30-day MACE, T3, adjusted OR 4.49, 95% CI 2.06-9.79; P < 0.001). Trimethyllysine in combination with TMAO showed additive significance for near- and long-term CV events, including patients with 'negative' high-sensitivity Troponin T levels. In a multicentre Swiss Cohort (N = 1683) comprised of ACS patients, similar associations between TML and incident 1-year adverse cardiac risks were observed (e.g. mortality, adjusted T3 HR 2.74, 95% CI 1.28-5.85; P < 0.05; and MACE, adjusted T3 HR 1.55, 95% CI 1.04-2.31; P < 0.05). Plasma TML levels, alone and together with TMAO, are associated with both near- and long-term CV events in patients with chest pain and ACS.

Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease: A CLARICOR trial sub-study

Background and aimsRaised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain. MethodsThe CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979). ResultsIn Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03–1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00–1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%). ConclusionsRaised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.

Gut Microbiota-Dependent Trimethylamine N-Oxide Predicts Risk of Cardiovascular Events in Patients With Stroke and Is Related to Proinflammatory Monocytes.

Objective- Gut microbiota-dependent metabolites, in particular trimethylamine N-oxide (TMAO), have recently been reported to promote atherosclerosis and thrombosis. Here, we examined for the first time the relation of TMAO and the risk of incident cardiovascular events in patients with recent first-ever ischemic stroke in 2 independent prospective cohorts. Moreover, the link between TMAO and proinflammatory monocytes as a potential contributing factor for cardiovascular risk in stroke patients was studied. Approach and Results- In a first study (n=78), higher TMAO plasma levels were linked with an increased risk of incident cardiovascular events including myocardial infarction, recurrent stroke, and cardiovascular death (fourth quartile versus first quartile; hazard ratio, 2.31; 95% CI, 1.25-4.23; P<0.01). In the second independent validation cohort (n=593), high TMAO levels again heralded marked increased risk of adverse cardiovascular events (fourth quartile versus first quartile; hazard ratio, 5.0; 95% CI, 1.7-14.8; P<0.01), and also after adjustments for cardiovascular risk factors including hypertension, diabetes mellitus, LDL (low-density lipoprotein) cholesterol, and estimated glomerular filtration rate (hazard ratio, 3.3; 95% CI, 1.2-10.9; P=0.04). A significant correlation was also found between TMAO levels and percentage of proinflammatory intermediate CD14++CD16+ monocytes ( r=0.70; P<0.01). Moreover, in mice fed a diet enriched with choline to increase TMAO synthesis, levels of proinflammatory murine Ly6Chigh monocytes were higher than in the chow-fed control group (choline: 9.2±0.5×103 per mL versus control: 6.5±0.5×103 per mL; P<0.01). This increase was abolished in mice with depleted gut microbiota (choline+antibiotics: 5.4±0.7×103 per mL; P<0.001 versus choline). Conclusions- The present study demonstrates for the first time a graded relation between TMAO levels and the risk of subsequent cardiovascular events in patients with recent prior ischemic stroke. Our data support the notion that TMAO-related increase of proinflammatory monocytes may add to elevated cardiovascular risk of patients with increased TMAO levels.

Are soccer matches dangerous for patients with heart disease? The HeartAtaque trial – A prospective pilot study

Abstract Introduction Behavioral and emotional factors are triggers of cardiovascular events (CVEs). It is uncertain whether soccer fans, particularly individuals with coronary artery disease (CAD), are at increased risk for CVEs. Objectives To assess the effect of watching soccer matches in patients with known CAD on the incidence of CVEs according to the match result. Methods We prospectively assessed 82 male soccer fans with a history of acute coronary syndrome during 23 matches of the 2015/2016 season. Each individual was assessed by Holter monitoring on the day of their team's match and on the control day. The primary endpoint was the composite of death, stroke, reinfarction, angina or sustained arrhythmia. Secondary endpoints assessed were episodes of non-sustained supraventricular or ventricular arrhythmia and mean heart rate (HR). Results Participants’ mean age was 61±10 years. Compared with the control day, despite a significant increase in HR (p 0.97), the number of CVEs did not differ according to the result (p>0.05). Moreover, the number of non-sustained episodes of supraventricular and ventricular arrhythmia did not differ when stratified according to the match result (p>0.05). Conclusions The match result was not associated with a difference in incidence of CVEs in patients with a past history of CAD, with ischemic and arrhythmic substrate, who watched soccer matches on television.

Jogos de futebol impróprios para cardíacos (HeartAtaque trial) – Estudo piloto prospetivo

IntroductionBehavioral and emotional factors are triggers of cardiovascular events (CVEs). It is uncertain whether soccer fans, particularly individuals with coronary artery disease (CAD), are at increased risk for CVEs. ObjectivesTo assess the effect of watching soccer matches in patients with known CAD on the incidence of CVEs according to the match result. MethodsWe prospectively assessed 82 male soccer fans with a history of acute coronary syndrome during 23 matches of the 2015/2016 season. Each individual was assessed by Holter monitoring on the day of their team's match and on the control day. The primary endpoint was the composite of death, stroke, reinfarction, angina or sustained arrhythmia. Secondary endpoints assessed were episodes of non‐sustained supraventricular or ventricular arrhythmia and mean heart rate (HR). ResultsParticipants’ mean age was 61±10 years. Compared with the control day, despite a significant increase in HR (p<0.001) that was independent of the result (p>0.97), the number of CVEs did not differ according to the result (p>0.05). Moreover, the number of non‐sustained episodes of supraventricular and ventricular arrhythmia did not differ when stratified according to the match result (p>0.05). ConclusionsThe match result was not associated with a difference in incidence of CVEs in patients with a past history of CAD, with ischemic and arrhythmic substrate, who watched soccer matches on television.

High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis.

Patients with RA display greater occult coronary atherosclerosis burden and experience higher cardiovascular morbidity and mortality compared with controls. We here explored whether pro-inflammatory cytokines and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, correlated with plaque burden and cardiovascular events (CVEs) in RA. We evaluated 150 patients with 64-slice coronary CT angiography. Coronary artery calcium, number of segments with plaque (segment involvement score), stenotic severity and plaque burden were assessed. Lesions were described as non-calcified, mixed or fully calcified. Blood levels of hs-cTnI and pro-inflammatory cytokines were assessed during coronary CT angiography. Subjects were followed over 60 (s.d. 26) months for both ischaemic [cardiac death, non-fatal myocardial infarction (MI), stroke, peripheral arterial ischaemia] and non-ischaemic (new-onset heart failure hospitalization) CVEs. Plasma hs-cTnI correlated with all coronary plaque outcomes (P < 0.01). Elevated hs-cTnI (⩾1.5 pg/ml) further associated with significant calcification, extensive atherosclerosis, obstructive plaque and any advanced mixed or calcified plaques after adjustments for cardiac risk factors or Framingham D'Agostino scores (all P < 0.05). Eleven patients suffered a CVE (1.54/100 patient-years), eight ischaemic and three non-ischaemic. Elevated hs-cTnI predicted all CVE risk independent of demographics, cardiac risk factors and prednisone use (P = 0.03). Conversely, low hs-cTnI presaged a lower risk for both extensive atherosclerosis (P < 0.05) and incident CVEs (P = 0.037). Plasma hs-cTnI independently associated with occult coronary plaque burden, composition and long-term incident CVEs in patients with RA. Low hs-cTnI forecasted a lower risk for both extensive atherosclerosis as well as CVEs. hs-cTnI may therefore optimize cardiovascular risk stratification in RA.

Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular Events in Patients With Type 2 Diabetes.

OBJECTIVEThe goal of this study was to determine whether plasma levels of advanced glycation end products (AGE) and oxidation products (OP) predict the incidence of cardiovascular disease (CVD) in type 2 diabetes.RESEARCH DESIGN AND METHODSFive specific AGE (methylglyoxal hydroimidazolone, carboxymethyl lysine, carboxyethyl lysine, 3-deoxyglucosone hydroimidazolone, and glyoxal hydroimidazolone) and two OP (2-aminoadipic acid and methionine sulfoxide [MetSO]) were measured at baseline in two intensive glucose-lowering studies: 1) a subcohort of the Veterans Affairs Diabetes Trial (VADT) (n = 445) and 2) a nested case-control subgroup from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n = 271).RESULTSIncreased levels of several AGE and OP were associated with older age, decreased kidney function, previous CVD, and longer diabetes duration, but not with hemoglobin A1c. In the VADT, increased risk of incident CVD events (n = 107) was associated with lower MetSO after adjusting for age, race/ethnicity, sex, prior CVD event, kidney function, treatment assignment, and diabetes duration (hazard ratio [HR] 0.53; 95% CI 0.28–0.99; P = 0.047). Individuals with both low MetSO and high 3-deoxyglucosone hydroimidazolone concentrations were at highest risk for CVD (HR 1.70; P = 0.01). In the ACCORD study, those with incident CVD events (n = 136) had lower MetSO (by 14%; P = 0.007) and higher glyoxal hydroimidazolone and carboxymethyl lysine (by 18% and 15%, respectively; P = 0.04 for both); however, only the difference in MetSO remained significant after adjustment for prior CVD event (P = 0.002).CONCLUSIONSLower levels of MetSO and higher levels of select AGE are associated with increased incident CVD and may help account for the limited benefit of intensive glucose lowering in type 2 diabetes.

Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study

Mineralocorticoid receptor (MR) antagonists are the recommended medical therapy for primary aldosteronism. Whether this recommendation effectively reduces cardiometabolic risk is not well understood. We aimed to investigate the risk of incident cardiovascular events in patients with primary aldosteronism treated with MR antagonists compared with patients with essential hypertension. We did a cohort study using patients from a research registry from Brigham and Women's Hospital, Massachusetts General Hospital, and their affiliated partner hospitals. We identified patients with primary aldosteronism using International Classification of Disease, 9th and 10th Revision codes, who were assessed between the years 1991-2016 and were at least 18 years of age. We excluded patients who underwent surgical adrenalectomy, had a previous cardiovascular event, were not treated with MR antagonists, or had no follow-up visits after study entry. From the same registry, we identified a population with essential hypertension that was frequency matched by decade of age at study entry. We extracted patient cohort data and collated it into a de-identified database. The primary outcome was an incident cardiovascular event, defined as a composite of incident myocardial infarction or coronary revascularisation, hospital admission with congestive heart failure, or stroke, which was assessed using adjusted Cox regression models. Secondary outcomes were the individual components of the composite cardiovascular outcome, as well as incident atrial fibrillation, incident diabetes, and death. We identified 602 eligible patients with primary aldosteronism treated with MR antagonists and 41 853 age-matched patients with essential hypertension from the registry. The two groups of patients had comparable cardiovascular risk profiles and blood pressure throughout the study. The incidence of cardiovascular events was higher in patients with primary aldosteronism on MR antagonists than in patients with essential hypertension (56·3 [95% CI 48·8-64·7] vs 26·6 [26·1-27·2] events per 1000 person-years, adjusted hazard ratio 1·91 [95% CI 1·63-2·25]; adjusted 10-year cumulative incidence difference 14·1 [95% CI 10·1-18·0] excess events per 100 people). Patients with primary aldosteronism also had higher adjusted risks for incident mortality (hazard ratio [HR] 1·34 [95% CI 1·06-1·71]), diabetes (1·26 [1·01-1·57]), and atrial fibrillation (1·93 [1·54-2·42]). Compared with essential hypertension, the excess risk for cardiovascular events and mortality was limited to patients with primary aldosteronism whose renin activity remained suppressed (<1 μg/L per h) on MR antagonists (adjusted HR [2·83 [95% CI 2·11-3·80], and 1·79 [1·14-2·80], respectively) whereas patients who were treated with higher MR antagonist doses and had unsuppressed renin (≥1 μg/L per h) had no significant excess risk. The current practice of MR antagonist therapy in primary aldosteronism is associated with significantly higher risk for incident cardiometabolic events and death, independent of blood pressure control, than for patients with essential hypertension. Titration of MR antagonist therapy to raise renin might mitigate this excess risk. US National Institutes of Health.