Predictor Of Future Cardiovascular Events Research Articles

Rest and stress aortic flow analysis by CMR in MyoFit46

Abstract Background Aortic stiffness is a strong predictor of future cardiovascular events and all-cause mortality. Aortic stiffness has never been measured during adenosine stress perfusion before, and may provide valuable relationship about this relationship. Aim To investigate if there are differences between aortic stiffness and conditions of rest and stress perfusion, in an older age-homogenous population-based cohort. Methods 203 participants from the longitudinal 1946 Medical Research Council National Survey of Health and Development British birth cohort were included. Cardiovascular Magnetic Resonance (CMR) imaging was performed at rest and during adenosine stress perfusion. 3 established and validated biomarkers of aortic stiffness were reported - pulse wave velocity, distensibility and beta stiffness, at rest and stress perfusion. All variables were non-normally distributed, therefore the Wilcoxon signed-rank test was used to look for significant differences between rest and stress. Results Aortic stiffness increased significantly during adenosine stress perfusion, shown by all biomarkers of aortic stiffness used: pulse wave velocity (p = <0.001), distensibility (p = <0.001), and beta stiffness (p = <0.001). However, the aortas of participants with a higher resting aortic stiffness at baseline were less dynamic (little if any aortic stiffness change with stress) when compared to those with low resting aortic stiffness. Conclusion It is feasible to measure aortic stiffness during adenosine stress perfusion. In healthy aortas, aortic stiffness increases in the acute phase of adenosine stress suggesting a new potential mechanism for the body response to adenosine – peripheral chemoreceptor reflex activation. Stiffer arteries at baseline are less modifiable and stress aortic flow CMR has the potential to identify these persons permitting early targeted therapy. Change in aortic stiffness, measured by stress aortic flow CMR is therefore a potential non-invasive biomarker of aortic health.

Searching for the Best Machine Learning Algorithm for the Detection of Left Ventricular Hypertrophy from the ECG: A Review.

Background: Left ventricular hypertrophy (LVH) is a powerful predictor of future cardiovascular events. Objectives: The objectives of this study were to conduct a systematic review of machine learning (ML) algorithms for the identification of LVH and compare them with respect to the classical features of test sensitivity, specificity, accuracy, ROC and the traditional ECG criteria for LVH. Methods: A search string was constructed with the operators "left ventricular hypertrophy, electrocardiogram" AND machine learning; then, Medline and PubMed were systematically searched. Results: There were 14 studies that examined the detection of LVH utilizing the ECG and utilized at least one ML approach. ML approaches encompassed support vector machines, logistic regression, Random Forest, GLMNet, Gradient Boosting Machine, XGBoost, AdaBoost, ensemble neural networks, convolutional neural networks, deep neural networks and a back-propagation neural network. Sensitivity ranged from 0.29 to 0.966 and specificity ranged from 0.53 to 0.99. A comparison with the classical ECG criteria for LVH was performed in nine studies. ML algorithms were universally more sensitive than the Cornell voltage, Cornell product, Sokolow-Lyons or Romhilt-Estes criteria. However, none of the ML algorithms had meaningfully better specificity, and four were worse. Many of the ML algorithms included a large number of clinical (age, sex, height, weight), laboratory and detailed ECG waveform data (P, QRS and T wave), making them difficult to utilize in a clinical screening situation. Conclusions: There are over a dozen different ML algorithms for the detection of LVH on a 12-lead ECG that use various ECG signal analyses and/or the inclusion of clinical and laboratory variables. Most improved in terms of sensitivity, but most also failed to outperform specificity compared to the classic ECG criteria. ML algorithms should be compared or tested on the same (standard) database.

The Congestion "Pandemic" in Acute Heart Failure Patients.

Congestion not only represents a cardinal sign of heart failure (HF) but is also now recognized as the primary cause of hospital admissions, rehospitalization, and mortality among patients with acute heart failure (AHF). Congestion can manifest through various HF phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Among patients with AHF, achieving complete decongestion is challenging, as more than half still experience residual congestion at discharge. Residual congestion is one of the strongest predictors of future cardiovascular events and poor outcomes. Through this review, we try to provide a better understanding of the congestion phenomenon among patients with AHF by highlighting insights into the pathophysiological mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion.

The association of plasma connective tissue growth factor levels with left ventricular diastolic dysfunction in patients with overt hyperthyroidism.

Left ventricular (LV) diastolic dysfunction is an independent predictor of future cardiovascular events. Early detection of patients with LV diastolic dysfunction can improve clinical outcomes through active management. However, the assessment of diastolic function is very complicated, and there are currently lack of effective biomarkers to assess the risk of LV diastolic dysfunction. Connective tissue growth factor (CTGF) plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the associations between plasma CTGF level and the risk of LV diastolic dysfunction in this study and judge its effectiveness in diagnosing LV diastolic dysfunction. A total of 169 patients with overt hyperthyroidism were included. LV diastolic function was evaluated and the subjects were divided into normal LV diastolic function group and LV diastolic dysfunction group. Routine clinical medical data, biochemical data, thyroid related parameters and echocardiographic parameters were recorded for analysis. Compared with normal LV diastolic function group, the LV diastolic dysfunction group had higher age and BMI, as well as lower heart rate, lower serum albumin, lower eGFR, higher serum TgAb and BNP level, and the incidences of hypertension were also higher (all P <0.05). Circulating plasma CTGF levels in the LV diastolic dysfunction group were significantly higher (normal LV diastolic function group: 7.026 [5.567-8.895], LV diastolic dysfunction group: 8.290 [7.054-9.225] ng/ml, median [(Interquartile range)], P = 0.004); Compared with the lowest quartile group, the crude odds ratios (OR) of LV diastolic dysfunction in the second, third, and fourth quartile group were 3.207, 5.032 and 4.554, respectively (all P<0.05). After adjustment for the potentially confounding variables, the adjusted OR values of the third and fourth quartile group had no obvious change. The results of ROC showed that the plasma CTGF had the largest area under the ROC curve, and the value was 0.659 (P = 0.005). The level of circulating plasma CTGF in the LV diastolic dysfunction group was significantly increased. Plasma CTGF level is an independent risk factor for LV diastolic dysfunction. Compared with serum BNP level, the plasma CTGF level may have auxiliary diagnostic value for LV diastolic dysfunction in hyperthyroid patients.

Artificial Intelligence in Coronary Artery Calcium Scoring Detection and Quantification.

Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such "incidental" CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.

Beyond the Basics: Unraveling the Complexity of Coronary Artery Calcification.

Coronary artery calcification (CAC) is mainly associated with coronary atherosclerosis, which is an indicator of coronary artery disease (CAD). CAC refers to the accumulation of calcium phosphate deposits, classified as micro- or macrocalcifications, that lead to the hardening and narrowing of the coronary arteries. CAC is a strong predictor of future cardiovascular events, such as myocardial infarction and sudden death. Our narrative review focuses on the pathophysiology of CAC, exploring its link to plaque vulnerability, genetic factors, and how race and sex can affect the condition. We also examined the connection between the gut microbiome and CAC, and the impact of genetic variants on the cellular processes involved in vascular calcification and atherogenesis. We aimed to thoroughly analyze the existing literature to improve our understanding of CAC and its potential clinical and therapeutic implications.

High mannose correlates with surrogate indexes of insulin resistance and predicts cardiovascular events independently of glycaemic status and traditional risk factors

Abstract Background Plasma mannose, an emerging marker of insulin resistance (IR), is independently associated with coronary artery disease and cardiovascular (CV) events, not only in patients with altered glycaemic status, but also among those with normal glucose tolerance (NGT) [1, 2]. Whether mannose is a predictor of future CV events is not known. Purpose To investigate the association of mannose with surrogate indexes of IR as well as with long-term prognosis in patients with and without dysglycaemia. Methods Fasting plasma mannose was measured by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS-MS) in 696 cases with a first myocardial infarction (MI) and 707 controls matched for age, gender and living area from the PAROKRANK study [3]. Subjects free of known diabetes were further categorized as having either NGT (n=1045) or newly detected dysglycaemia (i.e., impaired glucose tolerance or type 2 diabetes; n=358) according to the results of an oral glucose tolerance test (OGTT). Surrogate indexes of IR and insulin secretion were calculated using glucose, insulin and C-peptide levels measured at 0, 30 and 120 minutes during the OGTT. The relationship between plasma mannose and different indexes was explored by fitting univariate and multivariate linear regression models. Kaplan-Meier functions were used to estimate crude survival across mannose quartiles. Unadjusted and adjusted Cox proportional hazards models were used to investigate the prognostic capacity of mannose, categorized as high (top quartile) vs low (lowest three quartiles), in relation to major adverse cardiac events (MACE) defined as CV death, MI and stroke during 10 years of follow-up. Secondary outcomes were single components of MACE and all-cause mortality. Results Mannose levels were associated with indexes of IR independently of BMI and other covariates in both the NGT and dysglycaemia subgroups. There was no difference in crude MACE-free survival between subjects with high and low mannose (log-rank p=0.10; Figure 1). However, high mannose remained as the only predictor of MACE in the overall population (Hazard ratio (HR): 1.58 (1.10-2.27); p=0.014) after multiple adjustments (Figure 2). This association was independent of the presence of dysglycaemia (interaction p between mannose category and dysglycaemia group=0.94) and IR expressed as HOMA-IR. High mannose also predicted MI, independently of the presence of a first MI (HR: 1.62 (1.00-2.62); p=0.050), while there was no significant association with the other secondary outcomes. Conclusions In a case-control setting of first MI, high mannose was the only significant predictor of future CV events, independently of traditional CV risk factors including a previous MI, glycaemic state and IR. Our findings expand the knowledge indicating that mannose might be used as a clinical tool for CV risk stratification.

Baseline high sensitivity C-Reactive Protein predicts incident cardiovascular events and all-cause mortality in the ASCOT Study at 20-years

Abstract Introduction The prediction of future cardiovascular events in those at greatest risk is essential to optimise preventative therapies appropriately and effectively. The value of high sensitivity C-reactive Protein (hsCRP) has been questioned in this regard, and recent studies have suggested the utility of this widely assessed biomarker for predicting future mortality in those presenting with suspected myocardial infarction (MI), however the relationship in stable patients is still debated. Purpose To investigate the role of baseline hsCRP for predicting long-term incident cardiovascular events in hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), with follow-up extending to 20-years. Methods This ASCOT legacy study reports events after 20-years of the UK participants in the original ASCOT trial. ASCOT was a multicentre randomised trial, randomising patients with hypertension into amlodipine-based or atenolol-based blood pressure-lowering (BPL) treatment. In addition, those with total cholesterol &amp;lt;6.5 mmol/L and no previous lipid-lowering treatment underwent further randomisation to either atorvastatin or placebo as part of the lipid-lowering (LL) arm of ASCOT. We examined outcomes related to hsCRP levels in the LL arm, dichotomously (&amp;lt; or &amp;gt; 2mg/L), in tertiles or continuously, adjusting in Model 1 (age, sex, socio-economic status [years of education] and ethnicity) and Model 2 (Model 1 plus current smoker, body mass index, baseline systolic blood pressure, creatinine, diabetes, history of vascular diseases, history of antihypertensive medication and allocation to BPL and LL). All-cause mortality, non-fatal and fatal MI, total coronary events and procedures and total cardiovascular events were assessed. Results 5,294 participants were included in the final cohort, after exclusion of 3,286 participants in the LL arm (n=8,580) without hsCRP data. There were no substantial differences in baseline characteristics between treatment allocation arms (non-randomised, placebo or atorvastatin). The highest tertile of hsCRP (median [IQR], 6.41 [4.81-10.44]) strongly related to all-cause mortality, withstanding adjustment in both Model 1 (HR 95% CI, 1.38 [1.27-1.53]; p&amp;lt;0.001; p&amp;lt;0.001 for interaction) and Model 2 (HR 1.25 [1.10-1.42]; p&amp;lt;0.001; p&amp;lt;0.001 for interaction). Moreover, the highest hsCRP tertile also related to fatal and non-fatal MI (Model 2 – HR 1.32 [1.05-1.67]; p=0.020; p=0.019 for interaction); total coronary events and procedures (Model 2 – HR 1.27 [1.09-1.47]; p=0.002; p=0.003 for interaction); and total cardiovascular events (Model 2 – HR 1.22 [1.08-1.37]; p=0.001; p=0.001 for interaction). Conclusions This study demonstrates that one hsCRP reading at baseline independently predicts cardiovascular events and all-cause mortality at very long-term follow-up in patients at high-risk for these events, and may help stratify patients into higher risk categories for intensive preventative strategies.

Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance.

Among patients treated with statin therapy to guideline-recommended cholesterol levels, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is at least as strong a predictor of future cardiovascular events as is residual risk assessed by low-density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients with higher LDLC levels is uncertain but has implications for the choice of preventive therapies, including bempedoic acid, an agent that reduces both LDLC and hsCRP. The multinational CLEAR-Outcomes trial (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen Outcomes Trial) randomly allocated 13 970 statin-intolerant patients to 180 mg of oral bempedoic acid daily or matching placebo and followed them for a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and for all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse events after adjustment for traditional risk factors and randomized treatment assignment. Compared with placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months. Baseline hsCRP was significantly associated with the primary composite end point of major cardiovascular events (highest versus lowest hsCRP quartile; hazard ratio [HR], 1.43 [95% CI, 1.24-1.65]), cardiovascular mortality (HR, 2.00 [95% CI, 1.53-2.61]), and all-cause mortality (HR, 2.21 [95% CI, 1.79-2.73]). By contrast, the relationship of baseline LDLC quartile (highest versus lowest) to future events was smaller in magnitude for the primary composite cardiovascular end point (HR, 1.19 [95% CI, 1.04-1.37]) and neutral for cardiovascular mortality (HR, 0.90 [95% CI, 0.70-1.17]) and all-cause mortality (HR, 0.95 [95% CI, 0.78-1.16]). Risks were high for those with elevated hsCRP irrespective of LDLC level. Bempedoic acid demonstrated similar efficacy in reducing cardiovascular events across all levels of hsCRP and LDLC. Among contemporary statin-intolerant patients, inflammation assessed by hsCRP predicted risk for future cardiovascular events and death more strongly than hyperlipidemia assessed by LDLC. Compared with placebo, bempedoic acid had similar efficacy for reducing cardiovascular risk across hsCRP and LDLC strata. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993406.

Association of Uric Acid and Atherogenic Index Of Plasma in Diabetes Mellitus

Diabetes mellitus (DM) is a chronic disease characterized by insulin deficiency or peripheral resistance resulting in hyperglycemia. Diabetic patients have increased rates of coronary heart disease, cerebrovascular disease and peripheral vascular disease, and are two to three times more likely to develop cardiovascular disease (CVD). Serum uric acid (SUA) has been known to be associated with cardiovascular diseases. "Atherogenic index of plasma" (AIP) is considered to be a very sensitive predictor of future cardiovascular events. The study was done to evaluate the association of serum uric acid and atherogenic index of plasma in diabetic patients. A total of 315 diabetic patients were selected as study subjects based on predefined enrollment criteria. The patients were separated into groups according to their serum uric acid levels. Serum uric acid levels under 6 mg/dL were considered as normal. AIP was calculated as the logarithmically transformed ratio of triglyceride to high density lipoprotein cholesterol. The study found that AIP levels were significantly high in high SUA group compared to normal SUA group. The study showed a positive significant correlation between AIP and SUA (r=0.347, P&lt;0.001) in diabetes patients. Additionally, in binary logistic regression analysis, AIP was found to be independently associated with high UA levels. Present study reveals that SUA and AIP are closely related.&#x0D; Bangladesh J Med Biochem 2018; 11(2): 6-10

Doxorubicin-induced cardiovascular toxicity: a longitudinal evaluation of functional and molecular markers.

Apart from cardiotoxicity, the chemotherapeutic doxorubicin (DOX) induces vascular toxicity, represented by arterial stiffness and endothelial dysfunction. Both parameters are of interest for cardiovascular risk stratification as they are independent predictors of future cardiovascular events in the general population. However, the time course of DOX-induced cardiovascular toxicity remains unclear. Moreover, current biomarkers for cardiovascular toxicity prove insufficient. Here, we longitudinally evaluated functional and molecular markers of DOX-induced cardiovascular toxicity in a murine model. Molecular markers were further validated in patient plasma. DOX (4 mg/kg) or saline (vehicle) was administered intra-peritoneally to young, male mice weekly for 6 weeks. In vivo cardiovascular function and ex vivo arterial stiffness and vascular reactivity were evaluated at baseline, during DOX therapy (Weeks 2 and 4) and after therapy cessation (Weeks 6, 9, and 15). Left ventricular ejection fraction (LVEF) declined from Week 4 in the DOX group. DOX increased arterial stiffness in vivo and ex vivo at Week 2, which reverted thereafter. Importantly, DOX-induced arterial stiffness preceded reduced LVEF. Further, DOX impaired endothelium-dependent vasodilation at Weeks 2 and 6, which recovered at Weeks 9 and 15. Conversely, contraction with phenylephrine was consistently higher in the DOX-treated group. Furthermore, proteomic analysis on aortic tissue identified increased thrombospondin-1 (THBS1) and alpha-1-antichymotrypsin (SERPINA3) at Weeks 2 and 6. Up-regulated THBS1 and SERPINA3 persisted during follow-up. Finally, THBS1 and SERPINA3 were quantified in plasma of patients. Cancer survivors with anthracycline-induced cardiotoxicity (AICT; LVEF < 50%) showed elevated THBS1 and SERPINA3 levels compared with age-matched control patients (LVEF ≥ 60%). DOX increased arterial stiffness and impaired endothelial function, which both preceded reduced LVEF. Vascular dysfunction restored after DOX therapy cessation, whereas cardiac dysfunction persisted. Further, we identified SERPINA3 and THBS1 as promising biomarkers of DOX-induced cardiovascular toxicity, which were confirmed in AICT patients.

Arterial stiffness tested by pulse wave velocity and augmentation index for cardiovascular risk stratification in antiphospholipid syndrome.

Cardiovascular disease is a major cause of morbidity and mortality in Antiphospholipid syndrome (APS). Arterial stiffness (ArS) has emerged as a predictor of future cardiovascular events in the general population. We aimed to assess ArS in patients with thrombotic APS versus diabetes mellitus (DM) and healthy controls (HC) and identify predictors of increased ArS in APS. ArS was evaluated by carotid-femoral pulse wave velocity (cfPWV) and augmentation index normalized to 75 beats/min (AIx@75) using the SphygmoCor device. Participants also underwent carotid/femoral ultrasound for atherosclerotic plaque detection. We used linear regression to compare ArS measures among groups and assess ArS determinants in the APS group. We included 110 patients with APS (70.9% female, mean age 45.4 years), 110 DM patients and 110 HC, all age/sex matched. After adjustment for age, sex, cardiovascular risk factors and plaque presence, APS patients exhibited similar cfPWV [β = -0.142 (95% CI -0.514, 0.230), p = 0.454] but increased AIx@75 [β = 4.525 (95% CI 1.372, 7.677), p = 0.005] compared with HC and lower cfPWV (p < 0.001) but similar AIx@75 (p = 0.193) versus DM patients. In the APS group, cfPWV was independently associated with age [β = 0.056 (95% CI 0.034, 0.078), p < 0.001], mean arterial pressure (MAP) [β = 0.070 (95% CI 0.043, 0.097), p < 0.001], atherosclerotic femoral plaques [β = 0.732 (95% CI 0.053, 1.411), p = 0.035] and anti-β2-glycoprotein I IgM positivity [β = 0.696 (95% CI 0.201, 1.191), p = 0.006]. AIx@75 was associated with age [β = 0.334 (95% CI 0.117, 0.551), p = 0.003], female sex [β = 7.447 (95% CI 2.312, 12.581), p = 0.005] and MAP [β = 0.425 (95% CI 0.187, 0.663), p = 0.001]. APS patients exhibit elevated AIx@75 vs HC and similar to DM patients, indicating enhanced arterial stiffening in APS. Given its prognostic value, ArS evaluation may help to improve cardiovascular risk stratification in APS.

SERUM PROTEOMIC PROFILING OF CAROTID ATHEROSCLEROSIS: A POPULATION OUTCOME STUDY

Objective: Circulating proteins linked to atherosclerosis may improve cardiovascular (CV) disease prediction. Here, we applied proteomic profiling, feature selection and unbiased clustering to identify proteins associated with carotid atherosclerosis and integrate them in a protein-based classification system for prediction of future CV events. Design and method: 491 community-dwelling participants (mean age, 58±11 years; 51% women) underwent carotid ultrasonography and proteomic profiling (CVD II panel, Olink Proteomics) at baseline. Subsequently, we collected cardiovascular outcome for a median follow-up period of 10.2 years. We applied partial least squares (PLS) and a machine learning algorithm (Random Forest, RF) to identify proteins associated with carotid intima-media thickness (cIMT) and the presence of atherosclerotic plaques. Next, we assessed the association of future CV events with protein-based phenogroups defined by unbiased clustering (Gaussian Mixture modelling) based on influential proteins in PLS and RF. Results: Of 92 measured proteins, 13 were labelled as important by PLS and RF and were independently associated with cIMT and/or the presence of plaques after multivariable adjustment: pro-adrenomedullin, agouti-related protein, brother of CDO, CD40 ligand, CD84, GLO1, HB-EGF, HSP27, lipoprotein lipase, lymphotactin, PAR-1, PDGF subunit B and TGM2. Based on these proteins, the clustering algorithm subdivided the cohort into two distinct phenogroups. Compared to the first (n = 174), participants in the second phenogroup (n = 317) had: i) a more unfavourable lipid profile with higher total cholesterol and triglycerides and lower HDL cholesterol (P&lt;0.014 for all), but no differences in other CV risk factors such as age, blood pressure, smoking status and diabetes mellitus (P&gt;0.061 for all); ii) higher cIMT (P = 0.0020); and iii) a significantly higher risk for future CV events during follow-up (multivariable-adjusted hazard ratio (95% CI) versus cluster 1: 2.63 (1.25 to 5.56); P = 0.01). Conclusions: Carotid atherosclerosis was linked to proteins reflecting haemostasis, angiogenesis, blood pressure regulation and inflammation. Focused proteomic phenomapping adequately identified individuals at high risk for future CV events and may thus complement current CV risk stratification strategies.

The effects of nordic walking, high-intensity interval training, and moderate-to-vigorous intensity continuous training on arterial stiffness in patients with coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The investigator-initiated research was supported by the Innovations Fund of the Alternate Funding Plan for the Academic Health Sciences Centres of the Ministry of Ontario (PIs: Pipe, Reed) and Heart and Stroke Foundation of Canada (PI: Reid). Background Coronary artery disease (CAD) is a leading cause of mortality worldwide. Arterial stiffness, a process associated with aging, arteriosclerosis, and arterial remodeling, is a strong and independent predictor of cardiovascular and all-cause mortality in patients with CAD. Moderate-to-vigorous intensity continuous training (MICT) has been shown to improve arterial stiffness parameters, including pulse wave velocity (PWV, i.e., the speed at which arterial pressure waves travel along the aorta and large arteries) and augmentation index (AIx: i.e., aortic pressure waveform) in the CAD population. Yet, the role of alternative exercise training approaches on arterial stiffness in patients with CAD has not been elucidated. Our recent study demonstrated greater improvements following Nordic walking (NW) compared to high-intensity interval training (HIIT) and MICT in functional capacity, quality of life, and depression severity in patients with CAD. No previous trial has compared the efficacy of NW, HIIT, and MICT in improving arterial stiffness in patients with CAD. Alternatives to traditional MICT, such as NW and HIIT, may provide superior understudied benefits on vascular health in patients with CAD. Purpose We compared the effects of 12 weeks of NW, HIIT, and MICT on arterial stiffness in patients with CAD. Methods Patients with CAD were randomly assigned to: (1) NW (walking with NW poles at a resting heart rate [RHR] + 20–40 bpm), (2) HIIT (aerobic exercise equipment: 4 × 4-min of high-intensity work periods at 85%–95% peak HR), or (3) MICT (aerobic exercise equipment: RHR + 20–40 bpm) twice weekly for 12 weeks. At baseline and week 12, aortic stiffness parameters were measured using a non-invasive device by stroke volume (SV), total vascular resistance (TVR), AIx with and without normalization for a HR of 75 bpm (AIX@75), and PWV. Linear mixed-effects models with repeated measures were used to compare groups over time. Results A total of 130 patients with CAD (aged 61 ± 7 years; male: 85%) were randomized to NW (n = 43), HIIT (n = 43), or MICT (n = 44). Table 1 shows that significant main effects of time were observed for SV (∆: 5.485 m/L, F = 8.530, p = 0.004), with a time × group interaction (F = 3.710, p = 0.027) revealing a greater improvement in SV following NW compared to HIIT (F = 5.748, p = 0.019) and MICT (F = 5.494, p = 0.022). A significant time × group interaction (F = 3.700, p = 0.028) was observed in AIx@75, with a greater reduction following NW than MICT (F = 7.388, p = 0.008). No significant differences were observed in TVR, AIx, and PWV. Conclusion Our findings show that NW facilitated greater improvements in SV and AIx@75 parameters of arterial stiffness, an important predictor of future cardiovascular events, when compared to HIIT and MICT in patients with CAD. NW may be considered as an alternative exercise training to improve vascular health in those with CAD.

Systolic Blood Pressure and Pulse Pressure Are Predictors of Future Cardiovascular Events in Patients with True Resistant Hypertension.

Given the increased risk of cardiovascular events associated with resistant hypertension, predictive cardiovascular prognosis is extremely important. Ambulatory blood pressure monitoring (ABPM) is mandatory for resistant hypertension diagnosis, but its use for prognosis is scarce. This observational longitudinal study included 258 patients (mean age of 60.4 ± 11.2 years; 61.2% male), who underwent 24 h ABPM in a hypertension unit from 1999 to 2019. The outcomes were global cardiovascular events (cerebrovascular, coronary, and other cardiovascular events). The mean follow-up period was 6.0 ± 5.0 years. Sixty-eight cardiovascular events (61 nonfatal) were recorded. Patients who experienced cardiovascular events were generally older, with higher rates of chronic kidney disease and prior cardiovascular events. The 24 h systolic blood pressure (hazard ratio 1.44; 95% CI 1.10-1.88), night systolic blood pressure (1.35; 95% CI 1.01-1.80), and 24 h pulse pressure (2.07; 95% CI 1.17-3.67) were independent predictors of global cardiovascular events. Multivariate Cox analysis revealed a higher risk of future cardiovascular events, particularly in patients with a 24 h daytime and nighttime pulse pressure > 60 mm Hg with respective hazard ratios of 1.95; 95% CI 1.01-3.45; 2.15; 95% CI 1.21-3.83 and 2.07; 95% CI 1.17-3.67. In conclusion, APBM is a fundamental tool not only for the diagnosis of resistant hypertension, but also for predicting future cardiovascular events.

Arterial Stiffness as A Predictor of Future Cardiovascular Events: Methods of Measurement and Clinical Implications

Arterial stiffness has recently emerged as strong predictor of cardiovascular events, including coronary heart disease. The cardio-ankle vascular index (CAVI) is a novel index that measures the overall stiffness of the artery all the way from the point where it branches off from the aorta to the ankle. CAVI's ability to provide accurate results regardless of the patient's blood pressure at the moment of measurement is without a doubt its most valuable characteristic. CAVI is related to many cardiovascular risk factors, including hypertension, diabetes mellitus, dyslipidemia, and smoking. It also increases with age and in many arteriosclerotic diseases, such as coronary artery disease, carotid arteriosclerosis, chronic kidney disease, and cerebrovascular disease. CAVI also increases in patients who have cerebrovascular disease. Controlling conditions such as diabetes mellitus and hypertension, in addition to quitting smoking, may also reduce the risk of CAVI. This indicates that CAVI is a physiological surrogate measure of atherosclerosis, and it also implies that it might be a signal of lifestyle change. Recent research has shown that CAVI and numerous functions of the left ventricle are linked to one another, which points to a linkage between the heart muscle and vascular function. This study discusses the fundamentals of CAVI as well as our present understanding of the measurement, with a particular emphasis on its functions and potential future use.

Prognostic role of three-dimensional speckle-tracking echocardiography-derived left ventricular global longitudinal strain in cardiac amyloidosis: Insights from the MAGYAR-Path Study.

Systemic amyloidosis is an uncommon disorder in which amyloid fibrils deposit extracellularly. Three-dimensional speckle-tracking echocardiography (3DSTE) is a novel method able to assess left ventricular (LV) global longitudinal strain (GLS). Our aim was to evaluate the prognostic impact of 3DSTE-derived LV-GLS in patients with cardiac amyloidosis (CA). A total of 35 patients suffering from light-chain (AL) CA or transthyretin (TTR) CA were selected, but 7 patients had to be excluded due to insufficient image quality or were lost for follow-up. With AL-CA 23 cases, while for TTR-CA 5 patients were diagnosed. Complete two-dimensional Doppler and 3DSTE were performed in all subjects. The median follow-up was 201 days (ranging from 36 to 632 days) during which cardiovascular event was detected in 17 CA patients, including 8 cardiac deaths. Six patients were diagnosed with acute heart failure, two patients needed invasive interventions (percutaneous coronary intervention with stent-implantation, implantable cardioverter defibrillator implantation) and in one patient new higher grade atrioventricular block was registered. Using ROC analysis, 3DSTE-derived LV-GLS ≥11.8% (absolute value) was found to be a significant predictor for cardiovascular event-free survival (sensitivity 65%, specificity 64%, area under the curve 0.71, p=.05). Lower LV ejection fraction was confirmed in patients with LV-GLS <11.8% as compared to cases with LV-GLS ≥11.8%. In case of a cardiovascular event, LV-GLS was lower as compared to that of subjects with no events. Multivariable regression analysis confirmed that LV-GLS and LV end-diastolic diameter were independent predictors of cardiovascular survival. 3DSTE-derived LV-GLS is an independent predictor for future cardiovascular events in CA patients.

101 LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 IN STEMI VS NSTE-ACS PATIENTS: A MARKER OF CARDIOVASCULAR ATHEROSCLEROTIC RISK RATHER THAN THROMBOSIS

Abstract Background The precise role of Lipoprotein associated phospholipase A2 (Lp-PlA2) in the pathogenesis of acute coronary syndromes (ACS) and in the prediction of future cardiovascular events is still debated. So far, few data exist on the variations of Lp-PlA2 activity in ACS and especially in NSTE-ACS vs STEMI patients, where thrombotic and atherosclerotic mechanisms could play a differential role. The aim of the present study was, then, to compare Lp-PlA2 activity according to the type of ACS presentation. Methods A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed on blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay. Results We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p=0.05), displayed a lower rate of hypertension (p=0.002), previous MI (p=0.001) and PCI (p=0.01) and used less frequently statins (p=0.01) and clopidogrel (p=0.02). White blood cells and admission glycemia were increased in STEMI (p=0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p&amp;lt;0.001) and lower TIMI flow (p=0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132±41.1 vs 154.6 ±40.9 nmol/min/mL, p=0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs 57%, p=0.02, adjusted OR[95% CI]=0.20[0.06-0.68], p=0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r=0.47, p&amp;lt;0.001), but not with inflammatory biomarkers. Conclusion The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, and with recurrent cardiovascular events, therefore potentially representing a marker of a more aggressive atherosclerotic disease and higher cardiovascular burden and risk.

Ultra-Low-Dose Contrast Using Transluminal Renal Angioplasty: The ULTRA Study.

Although severe atherosclerotic renal artery stenosis (ARAS) is a predictor of future cardiovascular events, large trials have not shown the benefits of percutaneous transluminal renal angioplasty (PTRA). This study aimed to validate the safety and efficacy of PTRA using low-concentration digital subtraction angiography (LC-DSA) in patients with severe ARAS and advanced chronic kidney disease (CKD). This prospective study was conducted between August 2018 and October 2021. Eighteen patients with 20 lesions, CKD stage 3b or worse, and significant renal artery stenosis were included and underwent PTRA using ultra-low-dose contrast medium. The primary endpoint was a change in renal function based on serum creatinine (sCr) level. The mean sCr level significantly improved from 3.34 ± 1.8mg/dL pre-PTRA to 2.48 ± 1.19mg/dL at 1 month post-PTRA (P = .02). The mean amount of contrast used was 8.3 ± 3.9mL per vessel. More severe stenosis and rapid deterioration of renal function before treatment were associated with improved kidney function. No cardiovascular or renal complications such as stroke or contrast-induced nephropathy were observed during the 30-day period. PTRA using an ultra-low-dose contrast medium is safe and provides acceptable results.

Study protocol and baseline characteristics of Randomized trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and Eicosapentaenoic Acid: RESPECT-EPA, the combination of a randomized control trial and an observational biomarker study

Omega-3 polyunsaturated fatty acids (PUFAs) have been a hot topic since the Japan EPA Lipid Intervention Study (JELIS), the first landmark study using a highly purified eicosapentaenoic acid (EPA), indicated that EPA could decrease the incidence of cardiovascular events. Over 20 years have passed since the JELIS was conducted, and the standard treatment for dyslipidemia has altered significantly since then. The JELIS subjects did not undertake the current risk management especially current standard statins and did not exclusively target secondary prevention patients. In addition, the subjects included are relatively high EPA population. Furthermore, the clinical implication of the plasma EPA/arachidonic acid (AA) ratio as a biomarker has not yet been validated. Therefore, the Randomized trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy - Statin and EPA (RESPECT-EPA) was planned and is currently underway in Japan. The RESPECT-EPA comprises two parts: the open-label randomized controlled trial (RCT) and biomarker study (prospective cohort study design). The RCT included patients with a low EPA/AA ratio. These patients were then randomized to highly purified EPA (1800 mg/day) or control groups. The primary endpoint was cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, unstable angina pectoris, and clinically indicated coronary revascularization. The biomarker study assesses the EPA/AA ratio's usefulness as a biomarker for cardiovascular events prediction. In the RCT, a total of 2,460 patients were enrolled in 95 sites in Japan. Patients' baseline characteristics were similar between intervention and control groups in the RCT. The baseline median EPA/AA ratio was 0.243 and 0.235, respectively. A total of 1,314 patients were participated in the observational part, and the baseline median EPA/AA ratio was 0.577. After this study is completed, we will have further evidence on whether a highly purified EPA is effective in reducing cardiovascular events for secondary prevention or not, as well as whether if EPA/AA ratio is a predictor for future cardiovascular events. This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000012069).