Risk Of Future Cardiovascular Events Research Articles

High-sensitivity C-reactive protein use in cardiovascular risk screening at 6 to 12 months postpartum following hypertensive disorders of pregnancy

Patients with a hypertensive disorder of pregnancy are more likely to have underlying cardiovascular risk factors and are at increased risk of future cardiovascular disease. These patients are more likely to be diagnosed with new-onset chronic hypertension and meet the criteria for metabolic syndrome postpartum. High-sensitivity C-reactive protein is a marker of general inflammation and may be used to identify increased risk for cardiovascular disease. This collaborative data-sharing study between Yale University, United States (Yale Hearts Moms study) and Queen's University, Canada (Maternal Health Clinic) aimed to study the utility of high-sensitivity C-reactive protein in postpartum cardiovascular risk screening, as determined by 30-year risk (Framingham) and metabolic syndrome 6 to 12 months postpartum. Patients with a hypertensive disorder of pregnancy (n=478) or an uncomplicated, term pregnancy (n=90) had cardiovascular risk screening and risk scoring performed at 6 to 12 months postpartum. Patients were excluded if they had a multiple gestation or chronic hypertension, diabetes mellitus, or cardiovascular disease diagnosed before pregnancy. Patients were categorized according to high-sensitivity C-reactive protein (mg/L) into Normal (<3.0), High (3.1 to <10.0), and Acute (≥10.0) groups. The primary outcome of the study was risk for future cardiovascular events, calculated through surrogate measures such as hypertension and cholesterol. Kruskal-Wallis and chi-square tests were used to compare groups, with post hoc tests corrected using the Bonferroni method. Multivariable logistic regression was used to assess the association between high-sensitivity C-reactive protein and cardiovascular risk, adjusting for relevant medical and sociodemographic variables. Analysis was completed with IBM SPSS Statistics, version 27. Patients in the High and Acute high-sensitivity C-reactive protein groups were more likely to have a body mass index ≥30, to have experienced a hypertensive disorder of pregnancy, to have a lower household income, and to have not breastfed or to have breastfed for <6 months, when compared with the Normal high-sensitivity C-reactive protein group (all P<.05). Patients in the High and Acute high-sensitivity C-reactive protein groups had higher 30-year cardiovascular risk scores and were more likely to have metabolic syndrome when compared with the Normal high-sensitivity C-reactive protein group (all P<.05). Patients with High high-sensitivity C-reactive protein had 2-fold odds of metabolic syndrome 6 to 12 months after delivery, compared with those in the Normal high-sensitivity C-reactive protein group (adjusted odds ratio, 2.85 [95% confidence interval, 1.66-4.91]), adjusting for hypertensive disorder of pregnancy, body mass index, clinic site, breastfeeding, income, and family history of cardiovascular disease. Those with Acute high-sensitivity C-reactive protein also seemed to have elevated odds of metabolic syndrome compared with the Normal high-sensitivity C-reactive protein group (adjusted odds ratio, 2.52 [95% confidence interval, 1.24-5.12]). The odds of chronic hypertension were significantly higher (P<.05) in the High high-sensitivity C-reactive protein group (adjusted odds ratio, 1.72 [95% confidence interval, 1.12-2.65]) compared with the Normal group. Individuals with elevated postpartum high-sensitivity C-reactive protein are at increased risk of cardiovascular disease 6 to 12 months postpartum after a pregnancy complicated by a hypertensive disorder of pregnancy. Future research is critical to determine the most comprehensive and accurate method and timing of postpartum cardiovascular risk screening to decrease the incidence of preventable cardiovascular mortality among women.

Performance of a multi-biomarker panel for prediction of cardiovascular event in patients with chronic kidney disease

BackgroundPatients with chronic kidney disease (CKD) undergoing coronary catheterization are at increased risk of cardiovascular events (CVE). Measuring biomarkers before the procedure may guide clinicians in identifying patients at higher risk of future cardiovascular events. MethodsIn this sub-study the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA), 927 patients underwent coronary catheterization and were followed up for two years. Using machine learning algorithm and targeted proteomics from samples of patients with CKD, 4 biomarkers (kidney injury molecule-1, N-terminal pro B-type natriuretic peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) were integrated into a prognostic algorithm to predict CVE. Results from the panel are expressed in a graded fashion (CVE higher risk and lower risk) using a data-driven cutoff optimized for balanced sensitivity and specificity. ResultsDuring the 2-year follow-up, 74 CVE were ascertained. 51 (rate: 51/378 = 13.5%) events occurred in stage 1–2 CKD and 23 (rate: 23/68 = 33.8%) events occurred in stage 3–5 CKD. The C-statistic for predicting 2-years cardiovascular events in all 446 patients was 0.77 (0.72, 0.82). The model was well-calibrated (Hosmer-Lemeshow test p-value >0.40). Considering patients at CVE lower-risk within each CKD staging group as a reference, the hazard ratio (95% confidence interval) of cardiovascular events was 2.82 (1.53, 5.22) for CKD stage 1–2/CVE higher-risk, and 8.32 (1.12, 61.76) for CKD stage 3–5/CVE higher-risk. ConclusionMeasuring biomarker panel prior to coronary catheterization may be useful to individualize CVE risk assessment among patients with CKD.

Impact of persistent MVO late after STEMI on adverse left ventricular remodelling: a CMR study

Abstract Background Despite successful revascularization at the epicardial level, microvascular obstruction (MVO) appears soon after reperfusion in up to 50% of cases. Early MVO has been solidly associated with adverse resulting cardiac structure and heightened risk of future cardiovascular events. Although clinical and experimental studies demostrated the spontaneous repair of MVO, little is known about the occurrence and implications of persistent MVO late after infarction. Purpose We used cardiovascular magnetic resonance (CMR) to characterize the impact of persistent MVO late after reperfused ST-segment elevation myocardial infarction (STEMI) on adverse left ventricular (LV) remodelling (ALVR). Methods A prospective registry of 471 STEMI patients underwent CMR 7 [5–10] and 198 [167–231] days post infarction, and MVO (&amp;gt;1 segment) and ALVR (relative increase &amp;gt;15% at follow-up CMR) of LV end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) were determined. Results One-week MVO occurred in 209 patients (44%) and persisted in 30 of these (6%). Most patients with persistent MVO (22/30, 73%) displayed extensive (&amp;gt;2.5% of LV mass) MVO at 1 week. Compared with patients without MVO (n=262, 56%) or with MVO only at 1 week (n=179, 38%), those with persistent MVO at follow-up (n=30, 6%) showed higher rates of ALVR-LVEDVI (22%, 27%, 50% p=0.003) and ALVR-LVESVI (20%, 21%, 53% p&amp;lt;0.001). After adjustment, the extent (% of LV mass) of MVO at follow-up was independently associated with ΔLVEDVI (relative increase, %) (p=0.01) and ΔLVESVI (p=0.03). Compared to a 1:1 matched population of 30 patients with MVO only at 1 week, patients with persistent MVO more frequently displayed ALVR-LVEDVI (12% vs. 50%, p=0.003) and ALVR-LVESVI (12% vs. 53%, p=0.001). Conclusion MVO persists in a small percentage of patients in chronic phase after STEMI and exerts deleterious effects in terms of LV remodelling. These findings fuel the need for further research on microvascular injury repair. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” [grant numbers PI20/00637, PI15/00531, FI18/00320, and CIBERCV16/11/00486] and by Conselleria de Educaciόn – Generalitat Valenciana (PROMETEO/2021/008).

Outcomes following acute myocardial injury and type 2 myocardial infarction in patients with and without coronary artery disease

Abstract Background Acute myocardial injury and type 2 myocardial infarction typically occur in the setting of a concurrent illness. Differentiating acute myocardial injury from type 2 myocardial infarction is challenging as it relies on the assessment of myocardial ischaemia. Indeed, some have questioned whether this distinction is important, as patients with both conditions are at increased risk of future cardiovascular events. Whether this risk is similar and the role of identifying those with coronary artery disease is uncertain. Purpose To determine whether future risk of cardiovascular events and death differs in patients with type 2 myocardial infarction and acute myocardial injury according to the presence or absence of prior coronary artery disease. Methods We conducted a secondary analysis of a multi-centre randomised controlled trial of 48,282 consecutive patients with suspected acute coronary syndrome. Patients with an adjudicated index diagnosis of acute myocardial injury and type 2 myocardial infarction were stratified according to whether they were known previously to have coronary artery disease defined as prior coronary revascularisation, myocardial infarction, or angina. Cardiovascular death or myocardial infarction adjusted for the competing risk of non-cardiovascular death and all-cause death at one year was compared. Results In 9,115 patients with elevated cardiac troponin concentrations, 1,676 (18%) and 1,121 (12%) had acute myocardial injury and type 2 myocardial infarction, respectively. Patients with either condition known to have coronary artery disease were older (mean [standard deviation] age 78 [11] versus 73 [16] years) and more likely to be female (55% versus 45%) than those with no prior history. Coronary artery disease was previously identified in 40% (454/1,121) and 30% (509/1,167) of those with type 2 myocardial infarction and acute myocardial injury, respectively. Cardiovascular death or myocardial infarction at one year was more common in patients known to have coronary artery disease than those without for both acute myocardial injury (23% [115/509]) versus 14% [158/1,167]; P&amp;lt;0.001) and type 2 myocardial infarction (20% [91/454] versus 10% [69/667]; log-rank P&amp;lt;0.001) (Figure 1). Similarly all-cause death at one year was higher in patients with known coronary artery disease for both acute myocardial injury (31% [357/1,167] versus 18% [123/667]; P&amp;lt;0.001) and type 2 myocardial infarction (40% [115/509] versus 30% [135/454]; P&amp;lt;0.001) (Figure 2). Conclusion Coronary artery disease is recognised in around one third of patients with acute myocardial injury and type 2 myocardial infarction and is associated with higher rates of cardiovascular events and all-cause death. Risk doubled in those with coronary artery disease and was similar whether the index diagnosis was myocardial injury or infarction, suggesting that coronary investigation and secondary prevention may have a role in both conditions. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The University of Edinburgh and British Heart Foundation

LDL-C goal achievement and lipid-lowering therapy in patients by atherosclerotic cardiovascular disease subtype: the SANTORINI study

Abstract Background In the 2019 ESC/EAS guidelines, documented ASCVD is a criterion for patients being categorised as at very high cardiovascular (CV) risk, and stringent low-density lipoprotein cholesterol (LDL-C) reductions of ≥50% plus a goal of &amp;lt;1.4 mmol/L are recommended. Intensive lipid lowering therapy (LLT) is therefore key to reducing the risk of future CV events. Purpose To describe patient characteristics, approaches to lipid management and LDL-C goal attainment at baseline in the subgroup of secondary prevention patients with a history of ASCVD enrolled in the SANTORINI study. Methods SANTORINI is a multinational observational study (NCT-04271280) evaluating the real-world use of LLT in adult patients with high- and very-high CV risk enrolled from primary and secondary care sites across Europe between March 2020 and February 2021. The ASCVD status of patients was defined based on medical records as either coronary (myocardial infarction; unstable angina; angina pectoris; coronary artery bypass graft surgery; percutaneous transluminal coronary angioplasty; coronary artery disease [CAD]; CAD unequivocal on imaging), cerebral (stroke; transient ischaemic attack; cerebrovascular disease; cerebrovascular disease unequivocal on imaging; carotid artery disease), peripheral/other (peripheral arterial disease [PAD]; lower extremity artery disease; PAD unequivocal on imaging; retinal vascular disease; abdominal aortic aneurysm; renovascular disease) or polyvascular (≥1 ASCVD). Results Of the 9044 patients included in the analysis 6954 (76.9%) had a history of ASCVD. Baseline demographics and patient characteristics by type of ASCVD are shown in Table 1. The majority of patients were male (76.9%) and mean (SD) age was 66.1 (10.4) years. Mean (SD) LDL-C level was 2.29 (1.13) mmol/L and a total of 20.7% of patients achieved CV risk-based LDL-C goals. Fewer patients with cerebral ASCVD attained LDL-C goals (15.0%). Despite being at very-high CV risk, 21.4% of all patients had no documented LLT (up to 28.5% for the cerebral ASCVD group). The majority of patients (49.2%) received statin monotherapy, particularly moderate (21.8%) and high-intensity statins (24.9%). The peripheral/other ASCVD and cerebral ASCVD groups recorded the highest use of monotherapy across subgroups (≥57.8%), whereas any other LLT alone was consistently low, including ezetimibe (≤2.5%) and PCSK9i (≤2.0%). Overall, only 25.6% of patients received combination therapy (17.5% statin + ezetimibe; 4.7% PCSK9i + statin and/or ezetimibe; 3.4% other). Conclusion The SANTORINI baseline analysis shows that the majority of patients with ASCVD do not achieve their LDL-C goals. The underutilisation of combination therapy in this very high CV risk population highlights the need to move beyond high-intensity statin monotherapy and rather focus on combination therapies which achieve more intensive LDL-C reductions, thus improving LDL-C goal attainment. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany

Correlation between Cardiac Ultrasound Index and Cardiovascular Risk in Healthy Obese and Overweight Populations.

Objective To investigate the correlation of obesity and overweight with cardiac ultrasound parameters and future cardiovascular risk among healthy populations. Methods Basic clinical characteristics as well as cardiac ultrasound parameters were collected from healthy people. Firstly, all participants were divided into three groups: normal, overweight, and obese. Then the differences in cardiac ultrasound parameters between the three groups were calculated. Subsequently, those aged 35–60 years were screened to determine their cardiovascular risk according to the SCORE system. Finally, the correlation between cardiac ultrasound indices and cardiovascular risk was calculated. Results A total of 1328 healthy participants were included, of whom 504 were normal, 580 were overweight and 244 were obese. Obesity and overweight significantly increased the aorta, left atrium, right atrium, right ventricle, the end-diastolic diameter of the left ventricle, main pulmonary artery, right ventricular outflow tract, interventricular septum, left ventricular posterior wall, and triglycerides and decreased E/A values and high-density lipoprotein-cholesterol. Ejection fraction, fractional shortening, low-density lipoprotein-cholesterol, and total cholesterol did not change between the three groups. A total of 781 participants were screened for SCORE scores. Obesity and being overweight significantly increased the incidence of future cardiovascular events, and lower E/A values were also associated with cardiovascular risk. All cardiac parameters were strongly associated with cardiovascular risk. Conclusion Our research demonstrates that obesity and overweight can damage heart shape and function and raise the risk of future cardiovascular events in people that are healthy. Cardiovascular risk and cardiac structural and functional impairments are significantly positively correlated.

Neck circumference for predicting the occurrence of future cardiovascular events: A 7.6-year longitudinal study

Background & aimsThis study aimed to investigate whether neck circumference (NC) could be used to predict future cardiovascular (CV) events in a community-based Chinese cohort. Methods and resultsWe enrolled 1435 participants aged 50–80 years (men, 43.62%) from communities in Shanghai. High NC was defined as NC ≥ 38.5 cm in men and NC ≥ 34.5 cm in women. Kaplan-Meier analysis and Cox proportional hazards regression were performed to explore the association between NC and CV events. During a mean follow-up period of 7.6 years, 148 CV events (10.31%) occurred. The incidence of CV events was higher in men than in women (83 (13.26%) vs. 65 (8.03%), P = 0.002). Multivariable-adjusted Cox regression analysis showed that for every 1-SD increase in NC in the whole population, the hazard ratio (HR) of CV events was 1.45 (95% confidence interval [CI], 1.15–1.83). The dose-response association between NC and CV events was significant in men (HR, 1.37, 95% CI, 1.10–1.71) but not in women (HR, 1.19, 95% CI, 0.94–1.52). In comparison with participants showing low baseline NC, those with high baseline NC showed a significantly higher risk of CV events (HR, 1.59, 95% CI, 1.14–2.22). Further stratified by sex, the positive association remained significant in men (HR, 1.90, 95% CI, 1.21–2.98) but not in women (HR, 1.25, 95% CI, 0.75–2.07). ConclusionNC was significantly associated with the risk of future CV events in middle-aged and elderly populations in the community and was a better predictor in men.

332.10: Pre-transplant Coronary Angiography Findings Based on Coronary or Aorto-Iliac Calcification on CT Imaging in Asymptomatic Patients With a Negative Cardiac Stress Test

Purpose: Cardiac events are now the leading cause of early mortality after kidney transplantation. Long term exposure to immunosuppression also increases cardiometabolic stress after transplantation. Several studies in general population have shown that the presence of coronary artery calcification increases the risk of future cardiovascular events. Among pre-kidney transplant candidates, there remains wide variation in cardiac risk assessment practices across transplant centers. We report coronary angiography findings in asymptomatic candidates undergoing Kidney transplant evaluation with negative stress test but with findings of coronary or aorto-iliac calcification on CT imaging. Methods: We conducted a retrospective single center study of 76 Pre-Kidney transplant recipients who had a negative stress test and underwent coronary angiography between 2010 to 2021. All patients underwent coronary angiography based on coronary or aortoiliac calcification on CT imaging. Mean age was 60 years in both groups. Demographics and results are listed in table 1. Results: Results at our academic center showed that 18 out of 76 patients (23.6%) had a 70% stenosis in one or more coronary vessels. 11 out of 76 patients (14.4%) underwent single or multiple vessels stent placement and one underwent CABG. 7 out of 76 patients (9%) had significant distal disease or vessels were too small for intervention. In CAD group, 13 out of 18 patients (72%) were diabetic. All patients underwent successful kidney transplantation. Post Operative hypotension was more common in non-CAD group, in 9 patients as compared to 3 patients in CAD group. 5 patients in non-CAD recipients had post-op Atrial fibrillation Vs 1 in CAD group. Conclusions: In addition to traditional risk factors and other cardiac risk stratification modalities, Coronary or aorto-iliac calcification on CT imaging is a predictor of significant coronary artery disease in patients undergoing evaluation for kidney transplant surgery. coronary angiography before transplantation should be considered for potential candidates for Kidney transplant with negative stress test but significant vascular calcification. Table 1 - N=76 CAD=18 No CAD=58 Stent 11 NA CABG 1 NA Male/Female 12/6 34/24 Dialysis/Preemptive 12/6 46/12 DM 13 34 Former Smoker/ Nonsmoker 9/9 19/39 Months onHD (Mean) 32.2 32.4

Ultrasound Evaluation of Carotid Artery Intima-Media Thickness: Effective Early Marker of Carotid Artery Disease in Adult Head and Neck Cancer Patients After Neck Radiation?

Radiation is a recommended front-line treatment for many adult head and neck cancer (HNC) patients. Early identification of radiation-associated carotid artery disease (CAD), a well-known phenomenon, can minimize long-term sequelae. This integrative literature review assesses the use of ultrasound measured carotid artery intima-media thickness (IMT) as an early marker of CAD in adult HNC patients after neck radiation. A search of PubMed and Scopus databases in December 2020 yielded 475 unique articles published between January 2011 and December 2020, of which eight met inclusion criteria. Carotid IMT, measured by ultrasound, was significantly increased after neck radiation in all reviewed publications. Ultrasound was able to detect IMT measurements exceeding or at risk of exceeding pathologic IMT, indicating higher risk for future cardiovascular events. Findings suggest that radiation-associated carotid IMT increase occurs early and persists for years. Ultrasound adequately detects post-radiation carotid IMT changes and is a reliable early marker for radiation-associated CAD. Initiation of ultrasound screening should be considered prior to neck radiation for a baseline and at 1 year post treatment to optimize medical management.

Applications of cardiac biomarkers in chronic kidney disease.

Cardiovascular disease is the leading cause of death in individuals with chronic kidney disease (CKD). The mechanisms connecting CKD and cardiovascular disease are complex, and serum biomarkers can help improve our understanding. Nt-proBNP and troponin have documented success as biomarkers to diagnose and provide mechanistic insights in non-CKD populations. The purpose of this review is to summarize evidence suggesting efficacy and potential for clinical application of Nt-proBNP and troponin in individuals with CKD. Our understanding of how Nt-proBNP and Troponin should be interpreted in those with CKD is evolving. Although both biomarkers are in part cleared by the kidney, elevated levels predominantly reflect cardiovascular disease. Both Nt-proBNP and troponin are associated with risk for future cardiovascular events in CKD. Determining CKD-specific cutoffs and using biomarkers to guide therapy remains under active investigation. Of the many serum biomarkers under investigation, Nt-proBNP and troponin best meet the criteria for effective biomarkers in CKD. Assays are widely available and proven to be accurate in CKD populations. Nt-proBNP and troponin deserve special focus in ongoing research of cardiovascular risk reduction in CKD, especially to identify patients at the highest risk, suggest targetable mechanisms and assess treatment efficacy.

495 Use Of Coronary Calcium In Real-world Risk Profile Of Firefighters

Introduction: Coronary artery calcium score (CACs) is a powerful tool to predict the risk of future cardiovascular events in asymptomatic individuals. Studies have demonstrated that firefighters have a higher prevalence and severity of CAC than would be expected based on demographics and risk factors alone. However, the frequency of CAC in younger firefighters and its relationship to cardiac risk factors is not well defined.

Increased proteolytic cleavage of osteoglycin is associated with a stable plaque phenotype and lower risk of cardiovascular events

Background and aimsExtracellular matrix (ECM) remodeling is one of the key components in the formation of vulnerable atherosclerotic plaques and cardiovascular events. We recently showed that the full-length ECM-proteoglycan osteoglycin was associated with plaque vulnerability and future cardiovascular events. In the present study, we aimed to investigate the association of cleaved osteoglycin with plaque phenotype. MethodsTwo-hundred human carotid plaques were analyzed by immunohistochemistry. Cleaved osteoglycin and active caspase-3 were assessed by ELISA. ECM components (collagen, elastin and glycosaminoglycans) were assessed by colorimetric assays in plaque tissue homogenates. Matrix metalloproteinases (MMPs) were assessed using Milliplex. MMP-cleavage of osteoglycin and its effect on apoptosis were studied in vitro. Cardiovascular events were recorded during follow-up using national registries. ResultsPlaque levels of cleaved osteoglycin were significantly higher in asymptomatic plaques and correlated to α-actin plaque area, collagen, elastin and inversely to lipids, active.caspase-3 and a histological vulnerability index. Cleaved osteoglycin correlated to several MMPs, especially MMP-12, which was also shown to cleave osteoglycin in vitro. In vitro cleavage of osteoglycin was also associated with less smooth muscle cell apoptosis. Patients with high plaque levels of cleaved osteoglycin had a significantly lower risk to suffer from future cardiovascular events. ConclusionsThe current study shows that cleaved osteoglycin is associated with a stable plaque phenotype and lower risk for future cardiovascular events. Potentially due to reduced cell apoptosis and ability to retain LDL. These results indicate that targeting the cleavage of osteoglycin may be a potential therapeutic strategy to stabilize plaques.

Risk of cardiovascular events associated with pathophysiological phenotypes of type 2 diabetes.

Hyperglycaemia in type 2 diabetes is caused by varying degrees of two defects: low insulin sensitivity and beta-cell dysfunction. We assessed if subgrouping of patients into three pathophysiological phenotypes according to these defects could identify individuals with high or low risk of future cardiovascular events. This is a prospective cohort study. We assessed estimates of insulin sensitivity and beta-cell function from the homeostasis model assessment-2 in 4209 individuals with recently diagnosed type 2 diabetes enrolled from general practitioners and outpatient clinics in Denmark. Individuals were followed for a composite cardiovascular endpoint (either atherosclerotic outcomes (myocardial infarction, unstable angina pectoris, stroke, coronary or peripheral revascularization), heart failure, or cardiovascular death) and all-cause mortality. Totally 417 individuals with the insulinopenic phenotype (high insulin sensitivity and low beta-cell function) had substantially lower risk of cardiovascular events (5-year cumulative incidence: 4.6% vs 10.1%; age-/sex-adjusted hazard ratio (aHR): 0.49; 95% CI: 0.30-0.82) compared with 2685 individuals with the classical phenotype (low insulin sensitivity and low beta-cell function), driven by atherosclerotic events. Conversely, 1107 individuals with the hyperinsulinaemic phenotype (low insulin sensitivity and high beta-cell function) had more cardiovascular events (5-year cumulative incidence: 12.6%; aHR: 1.33; 95% CI: 1.05-1.69), primarily driven by increased heart failure and cardiovascular death and increased all-cause mortality. Simple phenotyping based on insulin sensitivity and beta-cell function predicts distinct future risks of cardiovascular events and death in patients with type 2 diabetes. These results suggest that precision medicine according to underlying type 2 pathophysiology potentially can reduce diabetes complications.

High-Density Lipoprotein Particle Subclasses in Statin-Treated Patients with Peripheral Artery Disease Predict Long-Term Survival.

Low-density lipoprotein-cholesterol reduction showed a strong reduction of cardiovascular (CV) event rates in CV disease. However, the residual risk of future CV events remains high, which especially extends to peripheral arterial disease (PAD). Nuclear magnetic resonance (NMR) spectroscopy offers a novel method for analysis of the lipoprotein spectrum. This study investigates lipoprotein subclasses using NMR spectroscopy and assesses implications for long-term survival in PAD. NMR spectroscopy was performed by Nightingale Inc., in 319 patients with stable PAD and well-controlled CV risk factors. Patients were followed-up for 10 years. During that period, 123 patients (38.5%) died, of those 68 (21.3%) were defined as CV deaths. Outcome data were analyzed by the Kaplan-Meier method and multivariable Cox-regression for lipoprotein particles. Small and medium high-density lipoprotein-particles (S-HDL-P and M-HDL-P) showed a significant inverse association with all-cause mortality in Cox-regression analyses after multivariable adjustment (S-HDL-P, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.57-0.88; M-HDL-P, HR: 0.72, 95% CI: 0.58-0.90) for each increase of one standard deviation. In contrast, cholesterol-rich X-large HDL-particles (XL-HDL-P) showed a positive association with all-cause mortality (HR: 1.51, 95% CI: 1.20-1.89). Only the association between XL-HDL-P and CV death sustained multivariable adjustment (HR: 1.49, 95% CI: 1.10-2.02), whereas associations for S-HDL-P and M-HDL-P were attenuated (HR: 0.76, 95% CI: 0.57-1.01; HR: 0.80, 95% CI: 0.60-1.06). This study shows a novel association for a beneficial role of S-HDL-P and M-HDL-P but a negative association with higher cholesterol-rich XL-HDL-P for long-term outcome in well-treated patients with PAD. Thus, these results provide evidence that NMR-measured HDL particles identify patients at high CV residual risk beyond adequate lipid-lowering therapy.

Temporal trends in abdominal aortic aneurysmal disease: a nationwide cohort study on cardiovascular morbidity and medical cardioprotective therapy.

Abdominal aortic aneurysmal disease is associated with increased risk of cardiovascular morbidity and death, which potentially can be reduced with cardioprotective medical therapy. The aim of this study was to observe temporal trends in prevalence and incidence of cardiovascular comorbidity as well as use of medical cardioprotective treatment in patients diagnosed with abdominal aortic aneurysmal disease. This was a population-based cohort study based on data from national health registries, including all patients diagnosed with abdominal aortic aneurysms between 1998 and 2018. Data were stratified into four time periods (1999-2003, 2004-2008, 2009-2013, and 2014-2018) to illustrate trends over time. Outcome measures were (i) cardiovascular comorbidity and medical cardioprotective therapy at time of diagnosis, (ii) new admissions for atherosclerotic cardiovascular disease, and (iii) all-cause mortality after 2-year follow-up. The study cohort included 33 296 individuals. Mean age was 74 years. Prevalence of atherosclerotic cardiovascular comorbidity at diagnosis decreased from 41.5 to 32.6%. Use of statins increased from 17.9 to 66.9%, antiplatelets from 45.6 to 63.3%, and combined therapy with both antiplatelets and statins from 11.3 to 44.8%, and from 12.1 to 50.7% when anticoagulant therapy was included. Developments in medication use plateaued after 2013. Prevalence and incidence of atherosclerotic cardiovascular disease decreased through all four time periods. The same applied to all-cause mortality, which decreased from 24.3 to 12.4 deaths (per 100 person-years). In patients diagnosed with abdominal aortic aneurysm, cardiovascular comorbidity at diagnosis, risk of future cardiovascular events, and all-cause mortality is decreasing. Nevertheless, cardiovascular burden and mortality rates remain substantial, and medical cardioprotective therapy can be further improved.

SUPERVISED AND UNSUPERVISED LEARNING TO DEFINE THE CARDIOVASCULAR RISK OF PATIENTS ACCORDING TO AN EXTRACELLULAR VESICLE MOLECULAR SIGNATURE

Objective: Secreted extracellular vesicles (EVs) are membrane-bound nanoparticles released from cells. Since their content reflect the specific signatures of cellular activation and injury, EVs display a strong potential as biomarkers in the cardiovascular (CV) field. We aimed at dissecting a specific EV signature able to stratify patients according to their CV risk and likelihood to develop fatal CV events. Design and method: A total of 404 patients were included in the analysis. For each subject, we evaluated several CV risk indicators (age, sex, BMI, hypertension, hyperlipidemia, diabetes, coronary artery disease, chronic heart failure, chronic kidney disease, smoking habit, organ damage) and the likelihood of fatal CV events at 10 years, according to the SCORE charts of the European Society of Cardiology. Serum EVs were isolated by immuno-capture and analyzed for the expression of 37 EV surface antigens by flow cytometry. Unsupervised and supervised learning algorithms were applied for clustering patients according to CV risk. Results: Based on expression levels of EV antigens, unsupervised learning classified patients into three clusters (cluster I, 288 patients; cluster II, 86 patients; cluster III, 30 patients). Prevalence of hypertension, diabetes, chronic heart failure and organ damage (defined as left ventricular hypertrophy and/or microalbuminuria) progressively increases from cluster I to cluster III, with an average 6.9-fold increase. Several EV antigens, including markers from platelets (CD41b-CD42a-CD62P), leukocytes (CD1c-CD2-CD3-CD4-CD8-CD14-CD19-CD20-CD25-CD40-CD45-CD69-CD86), and endothelium (CD31-CD105) were independently associated to the CV risk indicators and correlated to age, blood pressure, glucometabolic profile, renal function, and SCORE risk. EV specific signature obtained by supervised learning allowed the accurate classification of patients according to their 10-year risk of future CV events, as estimated with the SCORE risk charts. Conclusions: EV profiling, obtainable from minimally-invasive blood sampling, may be integrated into CV risk stratification, displaying a potential role in the tailored management of these patients.

Estimated cardiovascular benefits of bempedoic acid in patients with established cardiovascular disease

Background and aimsCardiovascular outcomes trials have demonstrated that lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk for future cardiovascular events. We assessed the potential cardiovascular benefits of bempedoic acid through a simulation study in patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C. MethodsThe validated SMART prediction model was used to estimate the baseline 10-year risk of three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) in patients with ASCVD who were enrolled in four Phase 3, randomized, placebo-controlled bempedoic acid studies. The predicted change in 10-year cardiovascular risk associated with bempedoic acid was estimated for each patient based on the Cholesterol Treatment Trialists’ model. Data were analyzed in two cohorts: Cohort 1 included mostly patients treated with moderate-high intensity statins, and Cohort 2 included patients who were intolerant of more than low-intensity statin. ResultsA total of 2884 patients were included in Cohort 1 and 226 in Cohort 2. Weighted average baseline 10-year cardiovascular event risk was 26.1% and 31.6% for Cohorts 1 and 2, respectively. The least squares mean percent difference (95% confidence interval (CI) of the predicted absolute change in 10-year cardiovascular event risk with bempedoic acid was −3.3% (−3.7% to −2.9%) for patients in Cohort 1 and -6.0% (−7.7% to −4.3%) for patients in Cohort 2 compared with placebo (p < 0.0001 for both). ConclusionsAmong patients with ASCVD who could potentially benefit from additional LDL-C lowering, our simulation predicted a lower absolute cardiovascular event risk after initiating bempedoic acid as compared with placebo.

STUDY OF ASSOCIATION OF INFLAMMATORY MARKERS WITH METABOLIC SYNDROME IN PREDIABETIC PATIENTS AT TERTIARY CARE CENTER OF RAJASTHAN, INDIA

Background: Metabolic syndrome (MS) is associated with the risk of developing cardiovascular disease and type 2 diabetes mellitus. The preferred clinical approach to cardiovascular prevention is to treat all the metabolic risk factors. Objective: The objectives is study of acute-phase reactants in MS patients. Methods: This study was conducted on 250 subjects and controls at Government Medical College and Associated Group of Hospitals Kota, Rajasthan from October 2019 to September 2021. The study group had 125 MS cases and an equal number of healthy controls. Demographic characteristic of all participants noted including age, sex, weight, and height. Results: We observed a significant rise in blood glucose, total cholesterol, S. triglyceride, S. low-density lipoprotein (LDL). S. Very LDL S. C-reactive protein (CRP), and ferritin level in MS cases when compared to control subjects, while serum high-density lipoprotein level found to be decreased in MS patients as compared to control group. Conclusion: In this study, both CRP and ferritin level are increased as the number of components of MS increased. Therefore, these inflammation parameters could accurately and timely discriminate patients with MS, according to IDF criteria, who are at increased risk for future cardiovascular events. There was a significant correlation between inflammation and the diabetic complications.

Innate Immune System Stimulation During Pregnancy Upregulates Thromboxane Synthesis in Rat Maternal Heart

BackgroundInfections during pregnancy are associated with adverse maternal and fetal outcomes. We previously showed that exposure to immunostimulatory CpG oligonucleotides (ODN2395, synthetic Toll‐like receptor 9 agonist) during pregnancy induces maternal vascular inflammation and enhances vascular tone in pregnant rats. These outcomes were mediated in part by activation of the cyclooxygenase/thromboxane A2 (COX/TxA2) pathway. The objective of this study was to investigate the impact of ODN2395‐induced immune system stimulation on maternal hearts during pregnancy.HypothesesExposure to TLR9‐mediated immune system activation during pregnancy upregulates the COX/TxA2signaling pathway in maternal cardiac tissues.MethodsRats were treated with a synthetic CpG DNA (ODN2395, 1 mg/kg, intraperitoneal injection) or vehicle (saline) in late pregnancy (gestational day (GD) 14, 16, and 18) and euthanized on GD 20 (term 22‐23). Fetoplacental biometrics were recorded after euthanasia and maternal hearts were collected to assess COX‐1 and COX‐2 expression via western blotting and 6‐keto PGF1α (PGI2 metabolic byproduct) and TxB2 (TxA2 metabolic byproduct) production use ELISA.ResultsMaternal heart weights did not differ between groups (ODN2395: 0.26 g/100 g BW vs. Vehicle: 0.23 g/100 g BW, n≥7, p=0.11). Left ventricular tissues from dams treated with ODN2395 released higher concentrations of TxB2compared to cardiac tissues from vehicle‐treated dams (ODN2395: 0.56 ± 0.06 ng/mg total protein vs. Vehicle: 0.31 ± 0.04 ng/mg total protein, n≥5, p=0.0041) but there were no differences in cardiac 6‐keto PGF1α release between groups (p=0.16). COX‐2 expression was lower in left ventricles from ODN2395‐treated rats compared to vehicle‐treated rats (p=0.009). There were no differences in cardiac COX‐1 expression between groups (p=0.27). Exposure to ODN2395 during pregnancy did not affect fetal weights (ODN2395: 2.28 ± 0.03 g vs. Vehicle: 2.25 ± 0.06 g, n≥7, p=0.9) or placenta weights (ODN2395: 0.44 ± 0.02 g vs. Vehicle 0.49 ± 0.01 g, n≥7, p=0.06), but increased fetal‐placental weight ratio (ODN2395: 5.3 ± 0.22 vs. Vehicle: 4.7 ± 0.15, p = 0.04). COX‐2 expression was greater in placental tissues from ODN2395‐treated rats (p=0.004) but there were no differences in placental 6‐keto PGF1α(p=0.51) and TxB2 production (p=0.32).ConclusionExposure to immunostimulatory CpG ODN during pregnancy induces upregulation of TxB2 synthesis in maternal cardiac tissues coupled with a reduction in COX‐2 expression. We suggest that cardiac inflammation during pregnancy may increase maternal risk for future cardiovascular events.

‘People say it is dangerous’

Introduction: Mild hypertension is a common asymptomatic condition present in people at low risk of future cardiovascular events. These people represent approximately two-thirds of those diagnosed with hypertension. The best available evidence does not support pharmacological treatment for mild hypertension to reduce cardiovascular mortality. Additionally, overdetection of hypertension also occurs, and this practice is supported by public awareness campaigns, screening, easy access to testing, and poor clinical practice, enhancing the overdiagnosis potential. Moreover, sparse qualitative patient-oriented evidence that diagnosing hypertension has harmful consequences is observed. Therefore, evidence regarding the potential for unintended psychosocial effects of diagnosing mild hypertension is required. Objective: The aim of this study was to investigate if diagnosing low-risk people with mild hypertension has unintended psychosocial consequences. Methods: Eleven semi-structured single interviews and four focus groups were conducted in São Paulo, Brazil, among people diagnosed with mild hypertension without comorbidities. Informants were selected among the general population from a list of patients, a primary healthcare clinic, or a social network. The informants had a broad range of characteristics, including sex, age, education level, race/skin colour, and time from diagnosis. Data were subjected to qualitative thematic content analysis by three of the authors independently, followed by discussions, to generate categories and themes. Results: The informants confirmed that the hypertension diagnosis was a label for psychosomatic reactions to stress, medicalised illness experiences, and set a biographical milestone. We observed unintended consequences of the diagnosis in a broad range of psychosocial dimensions, for example, fear of death, disabilities, or ageing; pressure and control from significant others; and guilt, shame, and anxiety regarding work and leisure. Although informants had a broad range of characteristics, they shared similar stories, understandings, and labelling effects of the diagnosis. Conclusion: The diagnosis of hypertension is a significant event and affects daily life. Most of the impact is regarded as negative psychosocial consequences or harm; however, sometimes the impact might be ambiguous. Patients’ explanatory models are key elements in understanding and changing the psychosocial consequences of the diagnosis, and healthcare providers must be aware of explanatory models and psychosocial consequences when evaluating blood pressure elevations.