Future Cardiovascular Research Articles

Ventricular-arterial coupling as assessed by the PWV/GLS ratio in the general population: reference values, correlates and predictive value

Abstract Purpose Ventricular-arterial coupling (VAC) reflects global cardiovascular efficiency. We may assess VAC state non-invasively by combining the non-invasive gold standards for arterial stiffness (carotid-femoral pulse wave velocity or PWV) and left ventricular systolic function (LV global longitudinal strain or GLS). To gain insight in the clinical value of the PWV to GLS ratio, we conducted a general population study to determine its reference values, clinical correlates and predictive value. Methods We measured PWV by applanation tonometry and GLS by echocardiography in 1026 individuals (mean age 50.3 years; 52% women). We derived age- and sex-specific reference values for PWV/GLS from a low-risk subsample. Clinical correlates of PWV/GLS were determined by stepwise regression. We calculated multivariable-adjusted hazard ratios (HR) for incident cardiovascular (CV) events (median follow-up time: 10.1 years). Results Upper limits of normality for PWV/GLS varied with sex and age, ranging from 0.41 m/sec% in young women up to 0.64 m/sec% in older men. Higher PWV/GLS correlated with male sex and higher age, heart rate, pulse pressure, mean arterial pressure and left ventricular mass (P<0.05 for all). On a continuous scale, only GLS was a significant predictor of CV events after adjustment (HR per 1% decrease: 1.24; P=0.0030). A PWV/GLS ratio above the median (>0.37 m/sec%) did predict future CV events after adjustment (HR versus below median: 2.02; P=0.0067). However, abnormal PWV/GLS defined by reference limits or by cutoffs from literature did not independently predict CV events (P≥0.31 for all). Conclusion Age- and sex-specific reference values for PWV/GLS were reported. PWV/GLS relates to age, sex and blood pressure. In contrast to GLS, PWV/GLS does not hold value for CV event prediction in the community.

Impact and consequences of the error of estimated GFR in patients with heart failure

Heart failure is a highly prevalent disease, which courses with frequent readmissions, mainly by Acute Heart Failure (AHF). Reduced renal function is associated with increased mortality in patients with HF. Therefore, an accurate and precise evaluation of renal function in patients with HF is crucial. The error of estimated GFR (eGFR) is wide and common, showing a ± 30% variability compared to measured GFR (mGFR). However, there is no evidence on the error of formulas in reflecting real renal function and particularly the consequences of this error in patients with AHF. This is a prospective study comparing the impact of mGFR versus eGFR in the onset of cardiovascular (CV) outcomes in patients with AHF. This was tested with cox survival analysis. Measured GFR was determined by the plasma clearance of iohexol-dbs and eGFR by Cockroft-Gould, MDRD, CKD-EPI creatinine, CKD-EPI cystatin-C and CKD-EPI creatinine + cystatin-C equations formulas. Also the agreement between mGFR and eGFR was analyzed. A total of 90 patients were included. Average age was 66 (± 12 years) and 52 (58%) were male. Of them 53 patients (59%) had a cardiovascular event during follow-up, 22 fatal (41%). The agreement between mGFR and eGFR indicated moderate precision and accuracy (concordance correlation coefficient of 0.77; CI = 0.73–0.82). In multiple cox survival analysis, mGFR was significantly associated with cardiovascular events together with NTproBNP, BMI, LVEF and previous coronary artery disease (p = 0.037; HR = 0.98, 95% CI = 0.95–0.99). Estimated GFR by formulas was not significant. In patients with AHF the error of formulas is large, frequent and random, also, mGFR and not eGFR predicted future CV events. The error of eGFR may have clinical consequences in specific subpopulations.

Association of R2-CHA2DS2-VASc score and clinical outcomes after bioprosthetic valve replacement: Subanalysis from BPV-AF registry

Abstract Background Although bioprosthetic valve (BPV) replacements are becoming more common, there are limited studies about prognostic prediction method for patients after BPV replacement. R2-CHA2DS2-VASc score is modified CHA2DS2-VASc score by adding reduced estimated glomerular filtration rate (eGFR < 60 mL/min/1.73m2). It is increasingly used for the prediction of cardiovascular (CV) events in patients with atrial fibrillation (AF), device implantation, and acute coronary syndrome. Purpose We aimed to evaluate the predictive value of R2-CHA2DS2-VASc score for future CV events in patients after BPV replacement. Methods BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients that underwent BPV replacement. Patients were stratified into three risk groups according to their R2-CHA2DS2-VASc score as follows; low (scores, 0–1), moderate (scores, 2–4), and high (scores, 5–11). The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure hospitalization, and cardiac death. Results A total of 766 patients were included in the analysis. The mean age was 80.3 years and 419 patients (54.7%) were female. Mean R2-CHA2DS2-VASc score was 4.1±1.5. Low, moderate, and high R2-CHA2DS2-VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. Median follow up period was 491 (interquartile range: 393-561) days. Kaplan-Meier analysis showed higher incidence of the composite CV events in high R2-CHA2DS2-VASc score group (Log rank test; p<0.01). Multivariate Cox proportional hazards regression analysis revealed that the R2CHA2DS2-VASc score as a continuous variable was an independent predictor of CV events (hazard ratio 1.33, 95% confidence interval 1.18 to 1.51, p<0.01). Conclusion The R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.Cumulative Incidence for Composite CV Ev

Troponin T as a risk marker for recurrent cardiovascular events in the post-discharge setting one month after acute coronary syndrome: a TRACER substudy

Abstract Background Troponin T (TnT) is a protein found in cardiac myocytes that is released during myocardial injury, such as myocardial infarction (MI). TnT levels rapidly rise during an MI, remain elevated for several days, and are a key criterion for diagnosing MI. Additionally, circulating TnT levels may offer prognostic information later, particularly during the rehabilitation phase after an acute coronary syndrome (ACS). Purpose To examine the relationship between circulating TnT at one month after hospitalisation for ACS and subsequent cardiovascular (CV) events. Methods The TRACER trial randomly assigned 12,944 patients diagnosed with non-ST-segment elevation ACS (NSTE-ACS) to receive either vorapaxar or placebo. Plasma samples were obtained after one month, and high-sensitivity (hs)-TnT was measured among 5,313 patients using the Elecsys electrochemiluminescence immunoassays. In this sub-study, the primary composite endpoint was the one-year risk of CV mortality, MI, or ischaemic stroke. Associations with outcomes were evaluated using Cox regression models, both unadjusted and adjusted for clinical baseline characteristics. Results The median concentration of hs-TnT was 11 ng/L one month after hospitalisation for ACS. Higher levels of hs-TnT at one month were associated with older age, coronary artery bypass surgery during the index ACS, male sex, a history of heart failure, renal disease, and diabetes mellitus. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 381 patients (incidence rate 5.4 per 100 person-years). Hs-TnT at one month after ACS was independently associated with the risk of the composite CV endpoint (relative hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 2.40 [1.80 – 3.20]) (see Figure 2). Similarly, hs-TnT, when added to a model including established risk factors, increased the concordance index of the multivariable model from 0.711 to 0.740 (p<0.001). The results were consistent across the different components of the composite endpoint. Conclusions The level of hs-TnT provides useful information on the risk of future CV events in patients when measured one month after an ACS. This information might be useful for optimising secondary preventive treatment following an ACS.Figure.Hs-TnT and composite CV outcome

Does Periodontitis Increase the Risk for Future Cardiovascular Events? Long-Term Follow-Up of the PAROKRANK Study.

The study 'Periodontitis and Its Relation to Coronary Artery Disease' (PAROKRANK) reported an association between periodontitis (PD) and the first myocardial infarction (MI). This follow-up study aims to test the hypothesis that those with PD-compared to periodontally healthy individuals-are at increased risk for cardiovascular (CV) events and death. A total of 1587 participants (age <75 years; females 19%) had a dental examination including panoramic radiographs between 2010 and 2014. PD was categorized as healthy (≥80% alveolar bone height), mild/moderate (79%-66%) or severe (<66%). A composite CV event (first of all-cause death, non-fatal MI or stroke and hospitalization following to heart failure) was investigated during a mean follow-up period of 9.9 years (range 0.2-12.5 years). Participants were divided into two groups: those with and without PD. The primary event rate, stratified by periodontal status at baseline, was calculated using the Kaplan-Meier method and Cox regression. The number of events was 187 in the 985 periodontally healthy participants (19%) and 174 in the 602 participants with PD (29%; p < 0.0001). Those with PD had a higher likelihood for a future event (hazard ratio [HR] = 1.26; 95% CI: 1.01-1.57; p = 0.038), following adjustment for age, smoking and diabetes. The PAROKRANK follow-up revealed that CV events were more common among participants with PD, which supports the assumption that there might be a direct relation between PD and CV disease.

Effect of Delayed Parathyroidectomy on Risk of Future Cardiovascular and Nephrolithiasis Interventions in Adults with Primary Hyperparathyroidism [Original Study

To determine whether the timing of parathyroid surgery impacts the risk of renal stone retreatment and cardiovascular interventions. Long-term, untreated primary hyperparathyroidism is associated with significant morbidity including nephrolithiasis and cardiovascular disease. We conducted a Population-based Cohort study of New York and California state-wide data from 2000-2020. Adult patients who underwent renal stone treatment and subsequently diagnosed with primary hyperparathyroidism (pHPT) and underwent parathyroidectomy (PTX) were included. Patients were excluded if PTX was prior to index stone procedure, they underwent second stone treatment within 6 months, with stage V CKD, with secondary or tertiary hyperparathyroidism, with prior kidney transplant or hemodialysis, or with prior cancer diagnosis. Rate of renal stone retreatment and cardiovascular interventions after PTX in pHPT patients with nephrolithiasis who underwent parathyroid surgery at ≤ 2 years and >2 years after index stone procedure was measured. We identified 2,093 patients who underwent first-time stone treatment and subsequent PTX. The median time to PTX was 560 days (IQR 187-1477) and follow-up was 7.4 years (IQR 4.5-13.1). Delaying PTX for more than 2 years increased the risk of renal stone retreatment by 59% (HR 1.59; P<0.001), increased the risk of experiencing coronary disease or associated interventions by 118% (HR=2.18; P=0.01), and increased the risk of experiencing an overall cardiovascular event by 52% (HR 1.52; P<0.01). In symptomatic pHPT, delaying PTX significantly increases the risk of requiring future stone retreatment and cardiac/vascular surgical interventions. This highlights the importance of early surgical referral and multidisciplinary approaches to optimize outcomes and resource utilization in pHPT.

Characterizing Vulnerability for the Future Heat-Related Cardiovascular Morbidity Burden in U.S. Metropolitan Areas

Characterizing Vulnerability for the Future Heat-Related Cardiovascular Morbidity Burden in U.S. Metropolitan Areas

Subclinical Atherosclerosis and Endothelial Dysfunction in Cases of Systemic Lupus Erythematosus: A Hospital-Based Case-Control Study.

Background Women are more likely to be affected with systemic lupus erythematosus (SLE), a chronic multisystem inflammatory autoimmune illness. It is well established that SLE increases the risk of cardiovascular (CV) events. This study aimed to determine the prevalence of endothelial dysfunction and subclinical atherosclerosis in patients with SLE. If these conditions are identified early, suitable preventative measures may be advocated to lessen the burden of future CV events. Aim This study aims to calculate the frequency of endothelial dysfunction and subclinical atherosclerosis in SLE patients using the flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thickness (c-IMT). Results There were 50 confirmed cases of SLE. Compared to healthy controls, SLE patients' c-IMT readings were higher, suggesting subclinical atherosclerosis. Thirty-three patients with c-IMT values >0.06 (p<0.00269) out of 50 SLE cases were found to have a high prevalence of subclinical atherosclerosis. Five SLE patients showed FMDs of less than 4.5% (p<0.021) compared to healthy controls, indicating preclinical atherosclerosis with endothelial dysfunction. It was discovered that endothelial dysfunction exhibited a positive linear connection with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) when contrasted with traditional inflammatory indicators such as ESRand CRP. Conclusion Patients with SLE face a higher risk of CV events and mortality compared to those without the condition. They are also more prone to developing endothelial dysfunction and subclinical atherosclerosis. Detecting these issues early can help in implementing primary and secondary prevention strategies effectively.

Artificial Intelligence-Enabled Electrocardiography Predicts Future Pacemaker Implantation and Adverse Cardiovascular Events.

Medical advances prolonging life have led to more permanent pacemaker implants. When pacemaker implantation (PMI) is commonly caused by sick sinus syndrome or conduction disorders, predicting PMI is challenging, as patients often experience related symptoms. This study was designed to create a deep learning model (DLM) for predicting future PMI from ECG data and assess its ability to predict future cardiovascular events. In this study, a DLM was trained on a dataset of 158,471 ECGs from 42,903 academic medical center patients, with additional validation involving 25,640 medical center patients and 26,538 community hospital patients. Primary analysis focused on predicting PMI within 90 days, while all-cause mortality, cardiovascular disease (CVD) mortality, and the development of various cardiovascular conditions were addressed with secondary analysis. The study's raw ECG DLM achieved area under the curve (AUC) values of 0.870, 0.878, and 0.883 for PMI prediction within 30, 60, and 90 days, respectively, along with sensitivities exceeding 82.0% and specificities over 81.9% in the internal validation. Significant ECG features included the PR interval, corrected QT interval, heart rate, QRS duration, P-wave axis, T-wave axis, and QRS complex axis. The AI-predicted PMI group had higher risks of PMI after 90 days (hazard ratio [HR]: 7.49, 95% CI: 5.40-10.39), all-cause mortality (HR: 1.91, 95% CI: 1.74-2.10), CVD mortality (HR: 3.53, 95% CI: 2.73-4.57), and new-onset adverse cardiovascular events. External validation confirmed the model's accuracy. Through ECG analyses, our AI DLM can alert clinicians and patients to the possibility of future PMI and related mortality and cardiovascular risks, aiding in timely patient intervention.

The Role Of Peri-coronary Fat Attenuation Index In Predicting Future Major Adverse Cardiovascular Events Across Baseline Cardiovascular Risk: Findings From A Large-scale Meta-analysis

The Role Of Peri-coronary Fat Attenuation Index In Predicting Future Major Adverse Cardiovascular Events Across Baseline Cardiovascular Risk: Findings From A Large-scale Meta-analysis

R2-CHA2DS2-VASc Score for Cardiovascular Event Prediction After Bioprosthetic Valve Replacement - Subanalysis From the BPV-AF Registry.

There are few studies evaluating the prognostic prediction method in atrial fibrillation (AF) patients after bioprosthetic valve (BPV) replacement. The R2-CHA2DS2-VASc score is increasingly used for the prediction of cardiovascular (CV) events in patients with AF, device implantation, and acute coronary syndrome. We aimed to evaluate the predictive value of the R2-CHA2DS2-VASc score for future CV events in AF patients after BPV replacement. The BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients who underwent BPV replacement. The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure requiring hospitalization, and cardiac death. A total of 766 patients was included in the analysis. The mean R2-CHA2DS2-VASc score was 5.7±1.8. Low (scores 0-1), moderate (scores 2-4), and high (scores 5-11) R2-CHA2DS2-VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. The median follow-up period was 491 (interquartile range 393-561) days. Kaplan-Meier analysis showed a higher incidence of the composite CV events in the high R2-CHA2DS2-VASc score group (log rank test; P<0.001). Multivariate Cox proportional hazards regression analysis revealed that the R2-CHA2DS2-VASc score as a continuous variable was an independent predictor of composite CV outcomes (hazard ratio 1.36; 95% confidence interval 1.18-1.55; P<0.001). The R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.

Blood clot properties, thrombin generation, and platelet activation in patients with dysglycemia and established atherosclerotic cardiovascular disease: The CASCARA study.

There is a strong link between coronary artery disease (CAD), type 2 diabetes (T2D) on one hand, and altered fibrin clot properties, including increased clot density, and unfavorable fibrin clot structure on the other. T2D-related changes in fibrin clots can increase cardiovascular (CV) disease risk, including future CV events. We aimed to assess fibrin clot properties, thrombin generation, and platelet activation in CAD patients with prediabetes (PD) or T2D, compared to CAD patients without glycemic disorders. We allocated patients to three groups: 1) Those with angiographically established CAD but without glycemic abnormalities (CAD group); 2) individuals with PD and established CAD (CAD+PD group); and 3) patients with T2D and CAD (CAD+T2D group). We conducted comparisons across these groups for thrombin generation, fibrin clot permeability, fibrin clot lysis, and platelet activation. The final analysis included 116 eligible patients: 1) CAD group (n = 31); 2) CAD+PD (n = 42); and 3) CAD+T2D (n = 43). The CAD+T2D patients enrolled had well-controlled T2D (median HbA1c level of 5.90%; IQR: 5.7%-6.3%). We found no significant differences in thrombin generation, fibrin clot properties, or platelet activation markers across the three analyzed groups (all P-values >0.20). However, elevated interleukin-6 (IL-6) levels were noted in both the highest and lowest glucose concentration quartiles. Additionally, a substantial increase in endogenous thrombin potential (ETP) was observed in patients in the highest glycated hemoglobin quintile. Individuals with established CAD and concomitant PD or well-controlled T2D exhibited comparable fibrin clot phenotypes, thrombin generation potential, and platelet activation when compared to CAD patients without dysglycemia.

Association of adverse pregnancy outcomes with cardiovascular risk profiles in later life: Current insights from the Hamburg City Health Study (HCHS)

Background and aimsAdverse pregnancy outcomes (APO) have been related to increased cardiovascular (CV) risk and mortality in later life. Underlying pathomechanisms for the development of CV disease in these women are not yet fully understood. In this study, we aimed to investigate the relationship between APO and individual CV risk profiles in later life. MethodsWe used cross-sectional data from 10,000 participants enrolled in the Hamburg City Health Study (HCHS). We analysed self-reported APO, CV risk factors and health status, including biomarkers, electrocardiogram, echocardiography and vascular ultrasound. To examine associations, Wilcoxon rank sum test and Pearson's χ2-test were performed. Multivariable-adjusted regression models were calculated to determine associations. ResultsN = 1970 women who reported pregnancies were included. Median age was 63 years, 8.7 % reported gestational hypertension (gHTN), 18 % excessive weight gain and 2.4 % gestational diabetes. Ten percent had delivered newborns with birth weight <2.5 kg, 14 % newborns with birth weight >4 kg. In multivariable-adjusted models, significant associations between APO, CV risk profiles and cardiac remodeling were identified. gHTN correlated with higher body mass index (BMI) (Beta 1.68, CI 95 % 0.86–2.50; p < 0.001), hypertension (OR 4.58, CI 95 % 2.79–7.86; p < 0.001), left ventricular remodeling (e.g. left ventricular mass index (Beta 4.46, CI 95 % 1.05–7.87; p = 0.010)) and myocardial infarction (OR 3.27, CI 95 % 0.94–10.07; p = 0.046). ConclusionsIn this population-based sample, APO were associated with CV risk profiles and cardiac remodeling in later life, suggesting early manifestations of future CV risk during pregnancy. Prospective data is needed for individual risk stratification in women with APO.

Serum Apolipoprotein-A2 Levels Are a Strong Predictor of Future Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention.

Because apolipoprotein-A2 (ApoA2), a key component of high-density lipoprotein cholesterol (HDL-C), lacks clear clinical significance, we investigated its impact on cardiovascular events in patients undergoing percutaneous coronary intervention (PCI).Methods and Results: We examined 638 patients who underwent PCI with a new-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoprotein levels measured between 2016 and 2021. The patients were divided into 2 groups based on the median serum ApoA2 values, and the incidence of major adverse cardiovascular events (MACE) was assessed. Of the 638 patients, 563 (88%) received statin treatment, with a median serum LDL-C level of 93 mg/dL. Furthermore, 137 patients (21.5%) experienced MACE, and Kaplan-Meier analysis revealed that the higher ApoA2 group had a significantly lower incidence of MACE than the lower ApoA2 group (30.9% vs. 41.6%). However, the other apolipoproteins, including ApoA1, ApoB, ApoC2, ApoC3, and ApoE, showed no significant differences in MACE. Multivariable Cox hazard analysis indicated that ApoA2 was an independent predictor of MACEs (hazard ratio, 0.666; 95% confidence interval, 0.465-0.954). Furthermore, ApoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (rs=-0.479). Among all the apolipoproteins, the serum ApoA2 level may be the strongest predictor of future cardiovascular events and prognosis in patients undergoing PCI.

Human epididymis protein 4 is a useful predictor of post-operative prognosis in patients with severe aortic stenosis.

The human epididymis protein 4 (HE4), a novel fibrosis marker, is expressed only in activated fibroblasts and is thought to reflect ongoing left ventricular (LV) fibrosis. LV fibrosis is a feature of severe aortic stenosis (AS) and is related to the post-operative outcome of patients with AS. We investigated the relationship between serum levels of HE4 and the post-operative prognosis of patients with severe AS. We measured the serum HE4 levels of 55 participants (80.8±8.0years old, male n=26, 46%) with severe AS prior to surgical aortic valve replacement (n=31, 56%) or transcatheter aortic valve implantation (n=24, 44%) at Kumamoto University Hospital in 2018. We followed them for cardiovascular (CV) death or hospitalization for heart failure (HF) for 3years. Serum HE4 levels were positively correlated with computed tomography-extracellular volume (CT-ECV) values (r=0.53, P=0.004). Kaplan-Meier curves demonstrated a significantly higher probability of hospitalization for HF or CV-related death in the patients with high HE4 (greater than the median HE4 value) compared with the patients with low HE4 (lower than the median HE4 value) (log-rank P=0.003). Multivariate analysis showed HE4 (log(HE4)) to be an independent prognostic factor [hazard ratio (HR): 7.50; 95% confidence interval (CI): 1.81-31.1; P=0.005]. Receiver operating characteristic (ROC) curve analysis suggested that HE4 is a marker of increased risk of CV-related death or hospitalization for HF at 3years after surgery, with an area under the curve (AUC) of 0.76 (95% CI: 0.62-0.90; P=0.003). We found that HE4 is a potentially useful biomarker for predicting future CV events in patients scheduled for AS surgery. Measuring serum HE4 values could help consider AS surgery.

Abstract 1087: Cardiovascular Risk Prediction By Platelet Transcriptomics

Background: Hyperreactive platelets are central to atherothrombotic events, including myocardial infarction (MI) and stroke. Currently, no routine clinical test can identify individuals with hyperreactive platelets. The development of a diagnostic platelet hyperreactivity test could identify patients most likely to benefit from antiplatelet therapy to reduce cardiovascular (CV) events. Aim: To develop a diagnostic tool to discriminate platelet hyperreactivity and CV risk. Methods: Platelet aggregation (0.4 μM epinephrine) was assessed by light transmission aggregometry (LTA) and responses &gt;60% were classified as “hyperreactive” and &lt;40% “normoreactive”. Simultaneously, platelet RNA was collected and sequenced (RNA-seq; n=88). Using machine-based learning, a hyperreactive platelet transcriptomic signature was identified, and a Platelet Reactivity ExpreSsion Score (PRESS) was assigned to each participant. Model training performance was evaluated by 10-fold cross-validation. Signature validation was performed in (a) control cohort without CV disease (n=35), and the diagnostic capacity of PRESS was assessed in patients (b) undergoing coronary angiography (n=28) and (c) lower extremity revascularization (LER, n=129). Results: PRESS successfully identified a hyperreactive platelet phenotype in patients with CV disease (AUC 0.81, 95% CI 0.68 - 0.94) and in an independent cohort of healthy participants off antiplatelet therapy (AUC 0.77, 95% CI 0.75 - 0.79). In patients undergoing diagnostic cardiac catheterization, PRESS was significantly higher in patients experiencing an acute MI (β=1.8, adj p=0.02). Among patients undergoing LER, those with a PRESS above the median were more likely to develop a future CV event (adj HR 1.90, CI 1.07 - 3.36, p=0.027). Conclusions: A platelet-derived transcriptomic signature identified individuals with hyperreactive platelets and was associated with increased CV risk. A diagnostic platelet reactivity score may facilitate a personalized approach to antithrombotic therapy for CV risk reduction.

Endodontic Inflammatory Disease and Future Cardiovascular Events and Mortality: A Report from the PAROKRANK Study

IntroductionProspective studies assessing the relation between endodontic inflammatory disease and subsequent cardiovascular events are few. The present aim was to explore associations between endodontic variables and future cardiovascular events in patients with myocardial infarction and matched controls participating in the PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study. MethodsEight-hundred five patients hospitalized for a first myocardial infarction and 805 controls were recruited between 2010 and 2014. Signs of endodontic inflammatory disease were assessed in panoramic radiographs taken at baseline. Mortality and morbidity data during the approximately 8 years of follow up were obtained from national registries. The risk for future cardiovascular events (first of mortality and nonfatal myocardial infarction, stroke, or hospitalization for heart failure) was analyzed with the log-rank test and Cox proportional hazards regression adjusted for the following confounders: sex, age, smoking, myocardial infarction, diabetes, education, marital status, family history of cardiovascular disease, and marginal periodontitis. ResultsIn total, 285 future events were observed during the follow-up period. Unadjusted analyses revealed that ≥1 root-filled tooth increased the risk of a future event. After adjustment, the number of remaining teeth and non–root-filled teeth decreased the risk of future events, whereas a higher Decayed, Missing and Filled Teeth score increased the risk and ≥1 primary apical periodontitis decreased the risk of suffering cardiovascular events. A higher Decayed, Missing and Filled Teeth score and decayed teeth increased the risk of all-cause mortality. ConclusionsTooth loss is a strong indicator of an increased risk for future cardiovascular events. Root-filled teeth seem of limited value as a risk indicator when accounting for other risk factors. The potential effect of dental interventions on future events should be assessed in future research.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Long-term Effects of Kidney Transplantation Compared With Dialysis on Intima-media Thickness in Children-Results From the 4C-T Study.

Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events. We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study. A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P = 0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate. IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk.

Role of High-sensitivity C-reactive Protein in Future Cardiovascular Events in Hemodialysis Patients.

The pathogenesis of cardio-vascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.