Risk Of Future Cardiovascular Events Research Articles

Coronary Microvascular Disease in Women: Epidemiology, Mechanisms, Evaluation, and Treatment.

Coronary microvascular dysfunction (CMD) involves functional or structural abnormalities of the coronary microvasculature resulting in dysregulation of coronary blood flow (CBF) in response to myocardial oxygen demand. This perfusion mismatch causes myocardial ischemia, which manifests in patients as microvascular angina (MVA). CMD can be diagnosed non-invasively via multiple imaging techniques or invasively using coronary function testing (CFT), which assists in determining the specific mechanisms involving endothelium-independent and dependent epicardial and microcirculation domains. Unlike traditional coronary artery disease (CAD), CMD can often occur in patients without obstructive atherosclerotic epicardial disease, which can make the diagnosis of CMD difficult. Moreover, MVA due to CMD is more prevalent in women and carries increased risk of future cardiovascular events. Successful treatment of symptomatic CMD is often patient-specific risk factor and endotype targeted. This article aims to review newly identified mechanisms and novel treatment strategies for managing CMD, and outline sex-specific differences in the presentation and pathophysiology of the disease.

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 study. MethodsEight-hundred and five patients hospitalized for a first myocardial infarction and 805 controls were recruited between 2010 to 2014. Signs of endodontic inflammatory disease were assessed in panoramic radiographs taken at baseline. Mortality and morbidity data during the approximately eight years of follow up were obtained from national registries. The risk for future cardiovascular events (first of mortality and non-fatal 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. Following adjustment, the number of remaining teeth and non-root filled teeth decreased the risk of future events while higher DMFT-score increased the risk and ≥1 primary apical periodontitis decreased the risk of suffering cardiovascular events. Higher DMFT-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.

A Study of Assessment of Preclinical Atherosclerosis by Carotid Intima-media Thickness in Newly Diagnosed Patients with Rheumatoid Arthritis Younger than 50 Years of Age and Their Correlation with Disease Activity: A Comparative, Cross-sectional Study

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition that has been linked to an increased risk of atherosclerosis and enhanced cardiovascular disease (CVD) risk. Most literature encompasses older age groups. Objectives: This study aimed to determine the carotid intima-media thickness (CIMT) in patients with newly diagnosed RA who are younger than 50 years of age and do not display the symptoms or traditional risk factors of CVD and compare it to the controls with same age and gender without RA. Furthermore, the correlation between CIMT and the disease activity Score -28 (Erythrocyte sedimentation rate) were examined. Subjects and Methods: The study enrolled 48 patients with RA and 51 healthy controls who met the study’s inclusion and exclusion criteria. All patients underwent CIMT by the ultrasound. Results: There was a significant increase in common carotid artery CIMT on both the right and left sides (P < 0.001) in RA patients as compared to controls. The correlations between CIMT (right and left) and DAS 28 ESR were only poor and negative. Conclusion: Younger patients with RA showed higher CIMT than age- and sex-matched controls, indicating an increased risk of future cardiovascular events even in the young.

Prediction of adverse cardiovascular events in children using artificial intelligence-based electrocardiogram

BackgroundConvolutional neural networks (CNNs) have emerged as a novel method for evaluating heart failure (HF) in adult electrocardiograms (ECGs). However, such CNNs are not applicable to pediatric HF, where abnormal anatomy of congenital heart defects plays an important role. ECG-based CNNs reflecting neurohormonal activation (NHA) may be a useful marker of pediatric HF. This study aimed to develop and validate an ECG-derived marker of pediatric HF that reflects the risk of future cardiovascular events. MethodsBased on 21,378 ECGs from 8324 children, a CNN was trained using B-type natriuretic peptide (BNP) and the occurrence of major adverse cardiovascular events (MACEs). The output of the model, or the electrical heart failure indicator (EHFI), was compared with the BNP regarding its ability to predict MACEs in 813 ECGs from 295 children. ResultsEHFI achieved a better area under the curve than BNP in predicting MACEs within 180 days (0.826 versus 0.691, p = 0.03). On Cox univariable analyses, both EHFI and BNP were significantly associated with MACE (log10 EHFI: hazard ratio [HR] = 16.5, p < 0.005 and log10 BNP: HR = 4.4, p < 0.005). The time-dependent average precisions of EHFI in predicting MACEs were 32.4%–67.9% and 1.6–7.5-fold higher than those of BNP in the early period. Additionally, the MACE rate increased monotonically with EHFI, whereas the rate peaked at approximately 100 pg/mL of BNP and decreased in the higher range. ConclusionsECG-derived CNN is a novel marker of HF with different prognostic potential from BNP. CNN-based ECG analysis may provide a new guide for assessing pediatric HF.

Cardiac Rehabilitation Using the Family-Centered Empowerment Model is Effective in Improving Long-term Mortality in Patients with Myocardial Infarction: A 10-year Follow-Up Randomized Clinical Trial.

Cardiac rehabilitation (CR) play a critical role in reducing the risk of future cardiovascular events and enhancing the quality of life for individuals who have survived a heart attack. To assess the mortality rates and stability of the effects in myocardial infarction (MI) survivors after implementing a Family-Centered Empowerment Model (FCEM)-focused hybrid cardiac rehabilitation program. This double-blind randomized controlled clinical trial, conducted at Shariati Hospital, an academic teaching hospital in Tehran, Iran (2012-2023), involved 70 MI patients and their families. Participants were randomly assigned to an FCEM intervention group or standard CR control group. The intervention commenced after the MI patient's safe discharge from the CCU and continued for the entire 10-year follow-up period. Various questionnaires were utilized to collect data on mortality rates and health-related quality of life (HRQoL). The 10-year follow-up period revealed lower mortality rates in the intervention group (5.7%, 11.4%, and 17.1% at 5, 7, and 10 years, respectively) compared to the control group (20%, 37.1%, and 48.9%). After adjusting for age, gender, and BMI, the control group had a four times higher mortality risk (HR: 4.346, 95% CI 1.671-7.307, P = 0.003). The FCEM-focused program demonstrated a significant and sustained positive impact on participants' quality of life for 48 months, with greater improvement compared to the control group. This study highlights the effectiveness of FCEM-based hybrid CR programs in enhancing long-term patient outcomes and reducing mortality rates among MI survivors. Further research is needed to explore the potential benefits in larger samples and diverse populations. This study (Identifier: NCT02402582) was registered in the ClinicalTrials.gov on 03/30/2015.

(015) Comparison of Penile Arterial Doppler-Ultrasound and Coronary Computed Tomography Angiography (CCTA) to Improve Cardiovascular Risk Assessment in Patients with Erectile Dysfunction

Abstract Introduction Erectile dysfunction (ED) has been shown to be an independent and early marker of future cardiovascular events, providing an important window of opportunity for cardiovascular preventive measures. However, there are several etiologies for ED (arterial, venous, hormonal, neurological, psychological), and earlier studies have not taken etiology into account when assessing cardiovascular risk. Arterial ED etiology share risk factors and pathophysiologic mechanisms with coronary and neurovascular diseases. Therefore, it can be assumed that patients with ED with arterial (atherosclerotic) etiology have a higher risk of future cardiovascular events than the general ED population. Objective To evaluate the predictive value of penile artery Doppler ultrasound (DUS) in cardiovascular risk assessment by comparing it with coronary atheroma screening by Coronary computed tomography angiography (CCTA) in patients with erectile dysfunction. Methods Men under 70 years of age, with ED and at least 1 cardiovascular risk factor (hypertension, dyslipidemia, diabetes, smoking, metabolic syndrome, obesity) were included. Patients with a primary cardiovascular event were excluded. Every patient had a penile DUS to assess penile arterial disease based on the maximum systolic velocity of the carvernous arteries after stimulation by intracavernous injection (A-Score), and a CCTA to assess coronary atheromatous arterial disease (CAD-RADS score). Results From October 2022 to June 2023, 72 consecutive patients were included. Mean age was 55 +/- 8.6 years. Mean IIEF5 score was 11 +/-5.3. N=34 (30%) were smokers, n=24 (33%) had hypertension, n=27 (37.5%) had diabetes, n=9 (11.1%) had obesity, n=10 (13.9%) had dyslipidemia. On penile artery DUS assessment n=62 (86%) patients had a positive A-Score. On CCTA, CAD-RADS scores were 0 in n=13 (18%) patients, 1 in n=18 (25%), 2 in n=19 (26%), 3 in n=17 (24%), and 4 in n=5 (7%) patients. We then analyzed the predictive value of A-Score as follows: 1. patients with coronary atheromatous plaques on CCTA (CAD-RADS ≥1, n=59), were significantly more likely to have a positive A-Score (n=56, 94.9%) than negative A-Score (n=13, 18%, p&amp;lt;.001, Chi2-test). The positive predictive value of the A-Score indicating penile arterial disease for the presence of coronary plaque, was 90.3%. 2. Patients with significant coronary stenosis (CAD-RADS ≥3, n=22) all patients n=22 (100%), had a positive A-Score and none a negative test (p=.026). The positive predictive value of the A-Score for the presence of significant coronary stenosis on CCTA was 100%. Conclusions The penile artery Doppler ultrasound A-Score has a good predictive value for coronary atheromatous artery disease in patients with erectile dysfunction, and allowed us to identify a sub-population at higher cardiovascular risk. When the A-Score is positive, the presence of coronary plaque is highly probable; when it is negative, the presence of significant coronary stenosis is highly unlikely. Disclosure No.

Association of plasma angiogenin with risk of major cardiovascular events in type 2 diabetes

BackgroundAngiogenin, an enzyme belonging to the ribonucleases A superfamily, plays an important role in vascular biology. Here, we sought to study the association of plasma angiogenin and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes (T2D).MethodsThis prospective study included 1083 T2D individuals recruited from a secondary hospital and a primary care facility. The primary outcome was a composite of four-point MACE (nonfatal myocardial infarction, stroke, unstable angina pectoris leading to hospitalization and cardiovascular death). Circulating angiogenin was measured by a proximity extension assay. Cox regression models were used to evaluate the association of baseline plasma angiogenin with the risk of MACE.ResultsDuring a median follow-up of 9.3 years, 109 (10%) MACE were identified. Plasma angiogenin was significantly higher in participants with MACE than in those without MACE (P < 0.001). Doubling of plasma angiogenin concentration was associated with a 3.10-fold (95% CI 1.84–5.22) increased risk for MACE. The association was only moderately attenuated after adjustment for demographic and cardiometabolic risk factors (adjusted HR 2.38, 95% CI 1.34–4.23) and remained statistically significant after additional adjustment for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (uACR) (adjusted HR 1.90, 95% CI 1.02–3.53). A consistent outcome was obtained when plasma angiogenin was analysed as a categorical variable in tertiles.ConclusionsPlasma angiogenin was associated with the risk of future cardiovascular events in patients with T2D and may be a promising novel biomarker for identifying high-risk T2D patients for early management.

Effect of chronic lung diseases on angina pectoris among Indian adults: longitudinal ageing study in India

The study aimed to evaluate the effect of chronic lung diseases, namely chronic obstructive pulmonary diseases (COPD) and asthma, on angina pectoris in individuals aged 45 years and above. Identifying vulnerable subpopulations suffering from COPD and asthma at higher risk of future cardiovascular events using the rose angina questionnaire is imperative for tailored primary and secondary prevention approaches. The present study utilizes the data from the Longitudinal Ageing Study in India, wave 1, conducted during 2017–2018. The sample size included 58,830 individuals aged 45 years and above. Angina was measured based on seven questions from Rose's questionnaires. Descriptive statistics and bivariate analysis were employed to examine the prevalence of angina among individuals with COPD and asthma. Further, multivariable logistic regression and propensity score matching (PSM) methods were used to assess the independent effect of COPD and asthma on angina after controlling the selected background characteristics. We employed PSM in two different models and included various additional factors in model 2, such as smoking, chewing tobacco, alcohol use, ADL, IADL, body mass index, physical activity, high cholesterol, hypertension, diabetes, and chronic heart disease. The current study shows that the prevalence of angina pectoris, COPD and asthma was 6.0%, 2.3% and 4.7%, respectively, among individuals aged 45 years and above in India. The prevalence of angina pectoris was higher among individuals with COPD (9.6% vs. 5.8%) and asthma (9.9% vs. 5.7%) than those without COPD and asthma, respectively. Additionally, angina pectoris was more prevalent among females and rural respondents with COPD (10.8% and 11.0%) and asthma (10.3% and 10.3%) compared to males and urban respondents with COPD (8.0% and 5.7%) and asthma (8.9% and 7.9%). Moreover, in the adjusted model, individuals with COPD (AOR 1.43, 95% CI 1.03 1.98) and asthma (AOR 1.44, 95% CI 1.17 1.77) had nearly 1.5-fold higher odds of having angina pectoris than those without COPD and asthma. The PSM estimates showed that individuals with COPD had 8.4% and 5.0% increased risk of angina pectoris compared to those without COPD in model 1 and model 2, respectively. We observed that, after adjusting to lifestyle, health-related and morbidity factors in model 2, both average treatment effect on untreated (ATU) and average treatment effect (ATE) values decreased by nearly 3.5%. Additionally, the PSM estimates demonstrated that individuals with asthma had a 3.4% and 2.9% increased risk of angina pectoris compared to those without asthma in model 1 and model 2, respectively. The study suggests that COPD and asthma are significantly associated with angina pectoris, and individuals with COPD and asthma have a higher risk of developing angina pectoris. Additionally, angina pectoris was more prevalent among females, rural respondents and adults aged 45–54 with COPD compared to males, urban respondents and those aged 65 and above, respectively, with COPD. Moreover, the findings of our study underscore the targeted primary and secondary interventions and team-based care approach among individuals with COPD and asthma to reduce the risk of CVD events in future.

InterVFast—effectiveness and acceptance of intermittent fasting in cardiac rehabilitation patients: study protocol of a randomized controlled trial

BackgroundResearch on intermittent fasting has shown that it can improve a variety of health outcomes, including blood sugar control, blood lipid levels and blood pressure. Only few studies document longer periods of fasting, especially in rehabilitation participants. Cardiac inpatient rehabilitation follows a multidisciplinary approach including change of health behaviour to reduce patients’ risk of future cardiovascular events. To date, evidence suggests that intermittent fasting can be an effective way to improve health and well-being, but more research is needed to fully understand its long-term effects and factors that promote the implementation. Therefore, the aim of the ongoing InterVFast trial is to investigate the effectiveness of intermittent fasting amongst cardiac rehabilitation patients after 4-week inpatient rehabilitation as well as 3 and 12 months subsequently including patients’ perspective.MethodsThis single-centre randomized controlled trial evaluates the effectiveness of the InterVFast intervention in weight loss (primary outcome). We also examine patients’ acceptance and the effect on relevant outcomes as blood glucose and triglyceride levels, cholesterol and high-sensitivity C-reactive protein. Weight, blood samples and clinical data are collected as part of the initial and final examination during inpatient rehabilitation. During inpatient rehabilitation, participants daily note fasting intervals and meals eaten as well as practicability in a fasting diary. In addition, interviews about perceived advantages and disadvantages and acceptance are carried out with the participants in the IG. A standardized follow-up examination (weight, blood samples) will be carried out by the family doctor after 3 and 12 months (t2 and t3).DiscussionCompared to other weight-loss intervention studies, our study addresses patients with coronary heart disease and includes patients’ acceptance as well as long-term maintenance. It is hypothesized that participation in the InterVfast intervention will improve relevant health outcomes in a sample of cardiac rehabilitation patients and thus constitute a behavioural prevention strategy to reduce the risk of future cardiac events and improve overall health and quality of life.Trial registrationClinicalTrials.gov DRKS00023983. Registered on February 17, 2022.

Ankle-Brachial Index: Diagnostic Tool of Peripheral Arterial Disease and Predictor of Cardiovascular Risk-An Update of Current Knowledge.

The ankle-brachial index (ABI) was introduced as a screening method for the diagnosis of lower extremity peripheral arterial disease (PAD). Later findings recognized ABI as a prognostic marker of adverse cardiovascular events due to its relation to atherosclerosis in other vascular territories. This narrative review aims to appraise the validity, reliability, and utility of ABI in the detection of PAD and the determination of global atherosclerotic cardiovascular risk. While the ABI value can be influenced by different physiological characteristics including age, sex, body position, and techniques used for ABI determination, it has high specificity and reproducibility in the assessment of vascular patients. In conclusion, when used correctly, the ABI remains a reliable and invaluable indicator of lower-limb perfusion and a useful tool for predicting the risk of future cardiovascular events. However, its underutilization in clinical settings is noteworthy.

Association between toothbrushing and cardiovascular risk factors: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2015–2017

BackgroundPrevious studies have suggested that frequent toothbrushing is associated with a lower risk of future cardiovascular events. We sought to investigate further the relationship between toothbrushing, cardiovascular risk factors, and lifestyle behaviours.MethodsWe analysed a cross-sectional survey including 13,761 adults aged 30 years or older without a history of cardiovascular diseases from the Korean National Health and Nutritional Examination Survey. Conventional cardiovascular risk factors (blood pressure, lipid profiles, and fasting glucose), and inflammatory markers (high-sensitivity C-reactive protein [hsCRP], and white blood cell counts [WBC]) were investigated in relation to the frequency of toothbrushing.ResultsThe estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort equations was 13.7%, 9.1%, and 7.3% for participants who reported toothbrushing 0–1, 2, and ≥ 3 times a day, respectively. Both conventional risk factors and inflammatory markers were significantly associated with frequent toothbrushing. However, after adjusting potential confounding factors such as age, sex, comorbidities, and lifestyle behaviours, only inflammatory markers were remained as significant factors.ConclusionsOral hygiene behaviours are closely linked to cardiovascular risk factors. This study suggests that reduced systemic inflammatory burden may explain the benefit of improved oral hygiene in terms of cardiovascular risk.

Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease.

Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.

Plasma levels of PRO-C3, a type III collagen synthesis marker, are associated with arterial stiffness and increased risk of cardiovascular death

Background and aimsThe N-terminal propeptide of type III collagen (PRO-C3) assay measures a pro-peptide released during type III collagen synthesis, an important feature of arterial stiffening and atherogenesis. There is a clinical need for improved non-invasive, cheap and easily accessible methods for evaluating individuals at risk of cardiovascular disease (CVD). In this study, we investigate the potential of using circulating levels of PRO-C3 to mark the degree of vascular stenosis and risk of cardiovascular events. MethodsBaseline plasma levels of PRO-C3 were measured by ELISA in subjects belonging to the SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort (N = 1354). Associations between PRO-C3 levels with vascular characteristics, namely stiffness and stenosis, and risk of future cardiovascular events were explored. Subjects were followed up after a median of 35 months (interquartile range 34–36 months), with recorded outcomes cardiovascular death and all-cause mortality. ResultsWe found a correlation between PRO-C3 levels and pulse wave velocity (rho 0.13, p = 0.000009), a measurement of arterial stiffness. Higher PRO-C3 levels were also associated with elevated blood pressure (rho 0.07, p = 0.014), as well as risk of cardiovascular mortality over a three-year follow-up period (OR 1.56, confidence interval 1.008–2.43, p = 0.046). ConclusionsElevated circulating PRO-C3 levels are associated with arterial stiffness and future cardiovascular death, in the SUMMIT cohort, suggesting a potential value of PRO-C3 as a novel marker for declining vascular health.

Cardiovascular Risk in Patients with Hematological Malignancies: A Systematic Review and Meta-Analysis

Patients with haematological malignancies (HM) are at risk of future cardiovascular (CV) events. We therefore conducted a systematic review and meta-analysis to quantify their risk of future CV events. We searched Medline and Embase databases from inception till 31 January 2023 for relevant articles using a combination of keywords and medical subject headings. Studies examining CV outcomes in patients with HM versus controls without HM were included. Outcomes of interest included acute myocardial infarction (AMI), heart failure (HF), and stroke. The outcomes were expressed as hazard ratios (HR) and their 95% confidence intervals (95% CI). This study is registered with PROSPERO at CRD42022307814. Fifteen studies involving 1,960,144 cases (178,602 patients with HM and 1,781,212 controls) were included in the quantitative analysis. Ten studies examined the risk of AMI, 5 examined HF, and 11 examined stroke. When compared with the control group, the HRs for HM for AMI, HF, and stroke were 1.65 (95% CI 1.29–2.09, p<0.001), 4.82 (95% CI 3.72–6.25, p<0.001), and 1.60 (95%CI 1.30–1.97, p<0.001) respectively. Sensitivity analysis of stroke risk based on lymphoma type showed an increased risk of stroke in patients with non-Hodgkin's lymphoma compared to controls (HR 1.31, 95% CI 1.04-1.64, p=0.03), but no significant difference for Hodgkin's lymphoma (HR 1.67, 95% CI 0.86-3.23, p=0.08). Patients with HM are at increased risk of future AMI, HF, and stroke, and these findings suggest that CV care of patients with HM should be considered as a growing priority.

Impact of acute kidney injury on major adverse cardiovascular events in intensive care survivors

BackgroundAcute kidney injury commonly occurs in patients admitted to ICU. After acute kidney injury, kidney function may not completely recover leading to increased risk of future cardiovascular events. We sought to ascertain the rates of cardiovascular events in ICU survivors and if these rates were affected by the presence of acute kidney injury whilst in ICU. MethodsThis retrospective observational cohort study utilised routinely collected data to identify patients who had survived an admission to one of two ICUs between July 2015 and June 2018. Baseline serum creatinine and subsequent values were used to identify acute kidney injury. Major adverse cardiovascular events described were myocardial injury, coronary artery intervention, or radiological evidence of stroke. ResultsOf the 3994 ICU survivors, major adverse cardiovascular events were identified in 385 patients (9.6%; 95% confidence interval [CI] 8.8–10.6%). Presence of acute kidney injury whilst in ICU was significantly associated with future major adverse cardiovascular events (hazard ratio=1.38; 95% CI 1.12–1.70; P-value=0.003) and future biochemical myocardial injury (hazard ratio=1.48; 95% CI 1.16–1.89; P-value=0.001). Acute kidney injury did not have a statistically significant association with future coronary artery interventions or future cerebrovascular events. ConclusionsOne in 10 ICU survivors experiences a major adverse cardiovascular event after discharge. Acute kidney injury whilst in ICU was associated with an increased risk of major adverse cardiovascular events and specifically myocardial injury. Further research is warranted on whether ICU survivors with acute kidney injury merit enhanced strategies for cardiovascular protection.

Integrative interpretation of cardiopulmonary exercise tests for cardiovascular risk stratification: a machine learning approach

Abstract Background and objectives Cardiopulmonary exercise testing (CPET) remains underutilized for cardiovascular (CV) risk assessment. Integrative interpretation of CPET results may improve characterization of cardiorespiratory fitness and assessment of CV risk. Therefore, we explored the clinical value of CPET-based phenomapping for CV risk stratification. Methods We retrospectively retrieved clinical data from 2280 patients with diverse CV risk (47.9% female) who underwent maximal CPET by cycle ergometry. We derived 18 key CPET indices as well as data on fatal and non-fatal CV events (median follow-up time: 5.3 years). Next, an unsupervised clustering algorithm (Gaussian Mixture modelling) subdivided the cohort in sex-specific phenogroups solely based on differences in CPET metrics. Clinical characteristics were compared across CPET phenogroups and their multivariable-adjusted association with future CV events was determined. Results 8 of the 18 CPET metrics were excluded from clustering due to high collinearity (i.e. an absolute Pearson correlation coefficient &amp;gt;0.8). Based on the remaining 10 CPET variables, the clustering algorithm subdivided the cohort in four male and four female CPET phenogroups. In both males and females, the phenogroups differed significantly in age, BMI, spirometric and CPET measurements and prevalence of hypertension, intake of antihypertensive and lipid-lowering drugs, CV disease and CV surgery (P&amp;lt;0.05 for trends). During follow-up, 278 males and 109 females experienced a CV event (43.9 and 16.2 events per 1000 years of follow-up, respectively). Compared to male phenogroup 1, male phenogroups 3 and 4 presented higher risk for incident CV events (multivariable-adjusted hazard ratio: 1.97 and 1.62; P≤0.027). Significant differences in risk for future CV events between the female phenogroups disappeared after adjustment for confounders. Conclusion Integrative CPET-based phenogrouping adequately stratified patients according to their risk for future CV events. Such phenomapping may facilitate comprehensive evaluation of CPET results and steer future CV risk management.Study flow and findings

Serum proteomic profiling of carotid atherosclerosis: a population outcome study

Abstract Background Circulating proteins reflecting atherosclerosis may improve cardiovascular (CV) disease prediction. We applied feature selection and unsupervised clustering on proteomic data to identify proteins associated with carotid atherosclerosis and construct a protein-based classification system for prediction of CV events. Methods 491 community-dwelling participants (mean age, 58±11 years; 51% women) underwent carotid ultrasonography and proteomic profiling (CVD II panel, Olink Proteomics). Subsequently, CV outcome was collected (median follow-up time: 10.2 years). We applied partial least squares (PLS) to identify proteins linked to carotid intima-media thickness (cIMT). Next, we assessed the association between future CV events and protein-based phenogroups derived by unsupervised clustering (Gaussian Mixture modelling) based on proteins influential in PLS. Results PLS marked 19 proteins as important, which were all associated with cIMT in multivariable-adjusted linear regression. 8 of the 19 proteins were excluded from the clustering due to high collinearity. Based on the 11 remaining proteins, the clustering algorithm subdivided the cohort into two phenogroups. Compared to the first (n=177), participants in the second phenogroup (n=314) presented: i) a more unfavourable lipid profile with higher total cholesterol and triglycerides and lower HDL cholesterol (P≤0.014); ii) higher cIMT (P=0.0020); and iii) a significantly higher risk for future CV events (multivariable-adjusted hazard ratio (95% CI) versus cluster 1: 2.05 (1.26 to 3.52); P=0.0093). The protein-based phenogrouping supplemented the ACC/AHA 10-year ASCVD risk score for prediction of a first CV event. Conclusions Phenogrouping based on a focused set of proteins related to carotid atherosclerosis identified individuals at high risk for future CV events. This approach may complement current CV risk stratification strategies.Summary of workflow and findingsCV event prediction

CAD-RADS score, vascular inflammation, and plaque vulnerability

Abstract Background Coronary artery disease reporting and data system (CAD-RADS), which is widely used to report the severity of coronary artery disease on coronary computed tomography angiography (CTA), predicts the risk of future cardiovascular events. However, the relationship between the CAD-RADS score and vascular inflammation and plaque vulnerability has not been investigated. Objective The aim of this study was to correlate the CAD-RADS score with vascular inflammation and plaque vulnerability. Methods This is an observational, single-center cohort study with prospective clinical follow-up. Patients who underwent both coronary CTA and optical coherence tomography (OCT) before coronary intervention were enrolled. All OCT and CTA images were analyzed at the core laboratory. Patients were categorized into two groups according to the CAD-RADS score (≤4a or 4b/5). All coronary arteries were analyzed for high-risk plaque features (positive remodeling, low-attenuation plaque, napkin-ring sign, and spotty calcification) and peri-coronary adipose tissue (PCAT) attenuation. PCAT attenuation was measured around the culprit lesion and in the proximal segment of all 3 coronary arteries. OCT features of plaque vulnerability were evaluated in culprit vessels. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as composite endpoints of unplanned target vessel revascularization, unplanned non-target vessel revascularization, nonfatal acute coronary syndrome, stroke, and cardiac death. Results Among 369 patients with 902 lesions, 104 (28.2%) were categorized in CAD-RADS 4b/5 and 265 (61.8%) in CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had higher PCAT attenuation than those with CAD-RADS ≤4a at all three levels (mean of 3 coronary vessels: -67.9 ± 6.9 HU vs. -70.2 ± 6.5, P=0.004; culprit vessel: -67.4 ± 7.9 vs. -70.2 ± 7.6, P=0.004; culprit plaque: -67.0 ± 9.3 vs. -69.9 ± 10.5, P=0.009; respectively) (Figure 1 A). Lipid-rich plaque and macrophage, as detected by OCT, were more prevalent in the culprit vessel in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (89.0% vs. 78.5%, P=0.001; 76.6% vs. 64.9%, P=0.001; respectively) (Figure 1B). All HRP features, as detected by CTA, were more frequently observed in patients with CAD-RADS 4b/5 than those with CAD-RADS ≤4a (P for all &amp;lt;0.001) (Figure 2). The cumulative incidence of MACCE was higher in patients with CAD-RADS 4b/5 than in those with CAD-RADS ≤4a (15.0% vs. 5.8%, P=0.045). Conclusions Higher CAD-RADS score was associated with a higher level of pan-coronary vascular inflammation and plaque vulnerability.Figure 1Figure 2

Guideline-directed low-density lipoprotein cholesterol management following acute ischemic stroke: findings from Clalit health services

Abstract Background Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated (2019) guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets after ischemic stroke are limited. Methods Data from a single national health care service on patients hospitalized with acute ischemic stroke between Jan. 2020 and Feb. 2022. Included were 3027 patients surviving ≥1-year post-stroke, with documented LDL-C levels and lipid-lowering medications at 2 timepoints (&amp;lt;3 months and during 6-12 months post-discharge). Participants were classified according to preexisting stroke and/or coronary artery disease (CAD). Results LDL-C levels &amp;lt;70 mg/dL and &amp;lt;55 mg/dL were attained by 42.3% and 22.9% of patients early post-hospitalization, and in 49.5% and 27.1% during 6-12 months post-hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in those with preexisting cardiovascular disease. The use of combination lipid-lowering therapy (ezetimibe and/or PCSK9 inhibitor plus statin) increased between the 2 timepoints: from 2% to 3.2% in those without prior stroke and/or CAD, and from 5.4% to 7% in those with prior stroke and/or CAD. Conclusions Despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies 6-12 months following hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Abstract 18385: Platelet Transcriptome in Type 2 Diabetes Provides Insight Into Peripheral Artery Disease and Cardiovascular Events

Background: Platelets are integral to atherothrombosis and peripheral artery disease (PAD), processes that are accelerated in diabetes. We evaluated the platelet transcriptome, generated a platelet RNA score, and investigated whether it could serve as a novel biomarker of PAD severity and major adverse cardiovascular events (MACE). Methods: We performed RNA sequencing on circulating platelet samples obtained from 133 patients enrolled in the platelet activity and cardiovascular events in PAD study. The transcriptome was (1) compared in PAD patients with Type 2 Diabetes (T2D) (n=73) vs without T2D (n=60), and (2) correlated with platelet aggregation responses to submaximal epinephrine (0.4uM). Using the overlap of transcripts identified by these approaches, we scored each sample based on a rank-based phenotypic metric (Singscore) to develop a T2D-specific platelet RNA score. This platelet score was compared in PAD patients with (vs without) critical limb ischemia (CLI), and PAD patients with (vs without) incident MACE (myocardial infarction, stroke, or death) after multivariable adjustment. Results: Overall, 384 transcripts were differentially expressed in PAD patients with vs without T2D (P&lt;0.01; 195 upregulated and 189 downregulated). Gene set enrichment analysis noted upregulation of pathways related to cell chemotaxis, acute inflammatory response, and platelet alpha granules in T2D. Among these 384 genes, 102 significantly correlated with platelet aggregation (P&lt;0.01) and were used to create a T2D platelet RNA score. To evaluate its clinical significance, this score was 3- times higher in PAD with (vs without) CLI (P=0.002). Further, after adjusting for age, sex, race, T2D, hypertension and coronary artery disease, the platelet score above (vs below) the median was associated with increased MACE (HR 2.8, 95% CI 1.4 to 5.6, P = 0.003). Conclusions: These findings demonstrate a unique platelet transcriptome in T2D that is associated with PAD severity and future risk of cardiovascular events. This work provides an important step toward the use of platelet RNA to unlock novel molecular mechanisms and inform future clinical outcomes.