Traditional Cardiovascular Risk Factors Research Articles

Circulating levels of Low Density Granulocytes and cell-free DNA as predictors of cardiovascular disease and bone deterioration in SLE patients.

The present work evaluates the predictive value of low-density-granulocytes (LDG) for the development of cardiovascular disease (CVD) and/or bone deterioration (BD) in a six-year prospective study in Systemic Lupus Erythematosus (SLE). Considering the high SLE-LDG capacity to form Neutrophil Extracellular Traps (NETs), circulating levels of total cell-free DNA (cirDNA) and relative amounts of mitochondrial and nuclear DNA (mtDNA and nDNA, respectively) were tested as LDG-associated biomarkers to identify SLE patients at risk of CVD and BD. To this end, the frequency of total blood LDGs, as well as the CD16negCD14neg (nLDG) and CD16posCD14low (pLDG) subsets, was quantified by flow cytometry in 33 controls and 144 SLE patients. Total cirDNA and relative amounts of mitochondrial (mtDNA) and nuclear (nDNA) cell-free DNA were measured by fluorometry or qPCR in plasma from a subgroup of 117 patients and 23 controls at enrolment. Our findings showed increased blood levels of SLE-nLDGs at enrolment associated with prospective CVD development (pCVD) and the presence of BD, thus revealing LDG expansion as a predictor of both comorbidities in SLE progression. The amounts of the different types of circulating DNA analysed were increased in patients, especially those presenting traditional CV-risk factors or subclinical atheromatosis. Similar to nLDGs, the nDNA concentration could predict the development of pCVD in SLE, supporting the quantification of cirDNA levels as a surrogate marker of LDGs in clinical practice.

Polygenic Risk Scores and Extreme Coronary Artery Calcium Phenotypes (CAC=0 and CAC≥1000) in Adults ≥75 Years Old: The ARIC Study.

Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age. There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans at visit 7 (2018-2019). In the primary analysis, an externally derived multi-ancestry polygenic CHD risk score was calculated for both White and Black participants. Results were confirmed using a separate ARIC-derived polygenic CHD risk score, including ≥6 million variants computed for White participants. We used multivariable logistic regression models to assess the association of polygenic CHD risk with CAC, after adjusting for baseline, time-averaged lifestyle, traditional risk factors, and local ancestry principal components. In the primary analysis, the average age was 80.6 years old, 61.6% were women, and the median CAC score was 246 (189 participants with CAC=0, 364 participants with CAC≥1000). Compared with persons below the 20th percentile of polygenic CHD risk, persons with polygenic-CHD risk above the 80th percentile had 82% lower odds of having CAC=0 (odds ratio, 0.18 [95% CI, 0.09-0.37]) and had >4-fold higher odds of CAC≥1000 (odds ratio, 4.77 [95% CI, 2.88-7.88]). On a continuous scale, each SD increment increase in the polygenic risk score was associated with a 78% higher CAC score. Results were nearly identical using a second confirmatory polygenic CHD risk score in White participants. Polygenic CHD risk is robustly associated with a lower prevalence of CAC=0 and a higher prevalence of CAC≥1000 in adults ≥75 years of age, beyond lifestyle and traditional risk factors. These results suggest a heritable contribution to distinct healthy and unhealthy arterial aging phenotypes that persist throughout the life course.

Abstract 4143289: Contemporary and Genomic Cardiovascular Risk Factors Have Explanatory Power Similar to Traditional Risk Factors for Incident Myocardial Infarction

Background: Modifiable cardiovascular risk factors (CRF) have been proposed to be responsible for 80-90% of the risk for incident coronary artery disease (CAD). However, these studies were conducted prior to the era of preventive medications, novel biomarkers, and genetic risk scores. The relative contributions of traditional and contemporary CRF in light of secular trends in worsening cardiometabolic health globally have not been assessed. Hypothesis: Including genetic risk scores and contemporary biomarkers will enhance discrimination and explainability of myocardial infarction (MI) incidence prediction. Methods: The UKBiobank was used to identify traditional CRF (hypertension, diabetes, dyslipidemia, smoking, waist-to-hip ratio (WHR), diet, exercise, alcohol intake and socioeconomic deprivation), and contemporary/genetic CRF (lipoprotein(a), high-sensitivity C-reactive protein [hsCRP], familial hypercholesterolemia [FH] variants, and polygenic risk score for CAD [PRS CAD ]). Incident MI was defined as first-time MI diagnosis or coronary revascularization. Base model discrimination was assessed using C-statistics from Cox proportional hazards models. Percent contribution of each risk factor was calculated by explanatory power lost via Nagelkerke R 2 after removal of the CRF from the full model. Population attributable risks (PAR) were additionally assessed for each model and CRF individually. Results: Over a median [IQR] follow-up of 11.0 [9.6, 12.5] years, 17409/299707 (5.8%) of participants developed incident CAD. C-statistics sequentially increased from base model to traditional CRF to contemporary/genetic CRF model with PAR of 84.3% (95% CI 82.4%-86.5%) ( Table 1 ). Among CRFs, hypertension (C 0.74, R 2 loss 15.2%, PAR 32.5%) and PRS CAD (C 0.72, R 2 loss 12.4%, PAR 38.4%) most strongly explained MI incidence by all 3 indices. Based on discriminability, ApoB:ApoA1 ratio (C 0.71, R 2 loss 3.4%), presence of diabetes (C 0.71, R 2 loss 2.2%), and log(hsCRP) (C 0.71, R 2 loss 1.82%) were subsequently prioritized. PAR analyses included prevalence in prioritization where WHR, presence of diabetes, and log(lipoprotein(a)) levels rose higher. Conclusions: The addition of genetic risk factors and contemporary biomarkers to explanatory models for CAD shows previously underappreciated importance of contemporary CRFs such as PRS, hsCRP, and lipoprotein(a) alongside traditional CRFs such as hypertension, dyslipidemia and presence of diabetes.

Abstract 4136289: Aortic Valve Calcium as a Predictor of Chronic Kidney Disease in a Multi-Ethnic Cohort: The MESA Study

Background: Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown. Objectives: To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease. Methods: We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m 2 . AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m 2 accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD. Results: Participants had a mean age 62.2±10.1 years, 53% were women, and AVC >0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10]; p = 0.005). There was a stepwise increased risk for CKD with higher AVC levels ( Figure ). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score ( p = 0.024), Lp (a) ( p = 0.004), and the APOE-ε4 genotype ( p = 0.004). Conclusions: In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.

Abstract 4136873: The Role of Socioeconomic Status in the Association Between Cardiovascular Polygenic Risk Score and Cardiovascular Events

Introduction: Polygenic risk scores (PRS) provide a summation of small-effect genetic variants that predict cardiovascular (CV) disease risk. Socioeconomic status (SES) can also impact CV risk, but it is unknown whether SES modifies the effects of PRS on CV events. Hypothesis: The association between CV PRS and CV events is modified by SES. Methods: Participants without CV disease at baseline from the UK Biobank prospective cohort study were followed from recruitment (2006-2010) through 2023. We included participants with genetic data (for CV PRS) and CV risk factors assessed at baseline (hemoglobin A1c, total cholesterol, blood pressure, body mass index, physical activity, tobacco use, and sleep). The CV PRS was centered at zero and standardized to one unit variance within each ancestry group. SES was defined by tertiles of index of multiple deprivation (from housing, crime, income, education, employment, health deprivation and disability, and neighborhood environment). The primary outcome was CV events (myocardial infarction, heart failure hospitalization, stroke, or death). Using Cox proportional hazard models, we estimated the total effect of PRS on CV events, tested for interaction of SES in the association between PRS and CV events, and estimated the direct effect of PRS on CV events by adjusting for age, sex, CV risk factors, and SES. Results: There were 201,374 participants (mean age 55.9 (± 8.1), 53.4% female). CV events occurred in 21,916 (10.9%) participants: 5,754 (2.9 %) myocardial infarctions, 4,061 (2.0%) strokes, 4,312 (2.1%) heart failure hospitalizations, and 12,782 (6.4%) deaths. Each unit of PRS was associated with 1.17 times the risk of CV events (HR 1.17, 95%CI 1.15 to 1.18, p-value < .001, adjusted for age and sex). People with the lowest SES had 1.22 times the risk of CV events (HR 1.22; 95%CI 1.18 to 1.26; p-value <.001) and the middle SES had 1.07 times the risk of CV events (HR 1.07; 95%CI 1.03 to 1.10; p-value <.001) compared to the highest SES, adjusted for age, sex, and CV risk factors. PRS remained associated with CV events (HR 1.15, 95%CI 1.13 to 1.16, p-value<.001) after adjusting for age, sex, CV risk factors, and SES. There was no significant multiplicative interaction between SES and PRS for CV events (interaction p-value = 0.45). Conclusions: SES is associated with CV events but does not modify the effect of PRS on CV events. Genetic risk remains independently important in CV event risk beyond traditional CV risk factors and SES.

Abstract 4118380: In-Hospital Outcome of Acute Heart Failure in Patients with Active Chronic Lymphocytic Leukemia

Introduction: Chronic lymphocytic leukemia (CLL) is prevalent among adults in Western countries, posing a significant health challenge due to its incurable nature and associated complications. Among these, cardiovascular disease, particularly heart failure (HF), has emerged as a major concern. Despite growing recognition, understanding of acute HF's epidemiology, outcomes, and risk factors in CLL patients remains limited. To address these gaps, we conducted a large-scale study using the National Inpatient Sample (NIS) database, aiming to examine acute HF prevalence, trends, outcomes, and predictors among CLL hospitalizations. Methods: We employed a retrospective cohort design utilizing NIS data from 2016 to 2021. CLL hospitalizations with and without acute HF were identified using ICD-10 codes. Our analysis included demographic characteristics, in-hospital outcomes, and multivariable logistic regression to identify predictors of outcomes. Propensity score matching was performed to mitigate confounding factors. Results: Among 423,829 CLL hospitalizations, 27.8% presented with acute HF. Patients with acute HF were older and had higher rates of comorbidities. While acute HF prevalence remained stable, in-hospital mortality increased over time, contrasting with stable rates among patients without acute HF. Acute HF was associated with higher mortality, cardiogenic shock, cardiac arrest, and major adverse cardiovascular events. Propensity score-matched analysis confirmed these associations. Discussion: Our study highlights acute HF as a common complication in CLL hospitalizations, linked with worse outcomes. The multifactorial nature of HF in CLL involves disease-related factors, treatment toxicities, and traditional cardiovascular risk factors. Prompt recognition and multidisciplinary management are essential for improving outcomes. Future research should focus on developing risk stratification tools and interventions targeting acute HF in CLL patients. Conclusion: Acute HF poses a significant burden on CLL hospitalizations, emphasizing the need for heightened awareness and tailored management strategies. Our findings underscore the importance of early recognition and intervention to improve outcomes in this vulnerable population.

Abstract 4136900: Left-to-right ventricular volume ratio as a predictor of cardiovascular events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The left ventricle (LV) and right ventricle (RV) are closely connected anatomically and functionally. Therefore, relative volume alterations signify pathologic disequilibrium even when within the normal range for chamber volumes. We aimed to define the prognostic value of volumetric imbalance between the LV and RV in the general population. Methods: The study sample consisted of 4073 asymptomatic participants from the Multi-Ethnic Study of Atherosclerosis who had a cardiac MRI at baseline. The left to right ventricular volume ratio (LRVR) was defined as LV volume/RV volume at end diastole. LRVR was categorized into balanced reference category 0.8-1.3, low (RV predominance) <0.8, and high (LV predominance) >1.3. Multivariable cox regression models were used to study the association between LRVR and heart failure (HF), atrial fibrillation (AF), and death. Results: The mean age of participants was 61.3±10 years, with 52% females. Participants were followed for a median of 17.8 years for HF, 16.7 years for AF, and 17.1 years for death. During follow up, 239 (5.9%) participants developed HF, 772 (19%) developed AF, and 906 (22.2%) died. When compared with the reference balanced LRVR group, those with high LRVR had increased risk of HF (HR 2.55; 95% CI 1.7-3.8; p <0.01), AF (HR 1.57; 95% CI: 1.2-2.06; p<0.01), and death (HR 1.63; 95% CI: 1.29-2.07; p<0.01) after adjusting for demographics and traditional cardiovascular risk factors. Participants with low LRVR had increased risk of HF (HR 1.88; 95% CI 1.1-3.2; p=0.02) and death (HR 1.51; 95% CI 1.12-2.04; p<0.01) in crude models. Adjusting for risk factors maintained increased risk of HF and death, but statistical significance was lost. Low LRVR was not associated with increased risk of AF. In a subgroup of participants with both absolute RV and LV volumes within normal ranges, high LRVR was still associated with increased risk of HF, AF, and death after adjusting for risk factors. Conclusion: In healthy asymptomatic participants at baseline, LV volume exceeding RV volume by at least 30% is associated with increased risk of HF, AF, and death. This relationship is independent of cardiovascular risk factors and absolute dilatation of either ventricle.

Abstract 4135861: Lipoprotein(a) and Its Impact on Left Ventricular Remodeling Over a Decade: The Multi-Ethnic Study of Atherosclerosis

Background: Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown. Objectives: This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease. Methods: 2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[<7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[>38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling ( Table ). Results: Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m 2 ; P = 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m 2 ; P = 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %; P = 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors ( Table ). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m 2 ; P = 0.01), LV indexed mass (β 1.17 g/m 2 ; P = 0.02) and a decrease in LV ejection fraction (β -1.01 %; P = 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 ( Table - Model 3), and baseline coronary artery calcium score and interim myocardial infarction ( Table - Model 4). Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Abstract 4113164: Central Arterial Stiffness in Young Adults with Perinatal HIV Exposure

Intro: Young adults with perinatally acquired HIV (YPHIV) have higher morbidity and mortality than uninfected persons. Antiretroviral therapy (ART) has extended life expectancy making adult CV disease a concern. Perinatal exposure to HIV increases inflammation which is associated with increased arterial stiffness which predicts CV disease. Aims: We compared arterial stiffness between YPHIV and young adults perinatally HIV exposed but uninfected (YPHEU), and evaluated the association of type and duration of ART regimens, HIV disease severity, and cardiac structure and function with arterial stiffness. Methods: In a substudy of the Pediatric HIV/AIDS Cohort Study, 150 participants (95 YPHIV, 55 YPHEU, mean 23.4 yrs, 60% female, 72% Black, 24% Hispanic) had echocardiography and pulse wave velocity (PWV) measured. We compared PWV between YPHIV and YPHEU, adjusting for covariates. Among YPHIV, we fit linear regression models to evaluate the association of current (within 1 year of PWV) and historical measures of HIV disease severity with PWV. We computed correlations between PWV and measures of left ventricular (LV) structure and function, overall and by HIV status. Results: Mean PWV and hemodynamic parameters did not differ between YPHIV and YPHEU (YPHIV 5.63 vs YPHEU 5.39 m/s; p=0.5). HIV control was good (82% with viral load <400 copies/ml), 91% used combination ART: integrase strand inhibitors (INSTIs; median duration 4.6 years), protease inhibitors (PIs 15.1 years), or non-nucleoside reverse transcriptase inhibitors (NNRTIs 5.2 years). Most participants had normal PWV compared to healthy controls but all values above 11.8 m/sec ( Figure , level associated with CV events in adults) were only in YPHIV. Only weak correlations were observed between PWV and echocardiographic measures (<0.20) in both YPHEU and YPHIV. Among YPHIV, HIV severity measures were not associated with PWV using either current or historical measures. Mean PWV was 1.68 (-0.36, 3.72) m/s higher among YPHIV with current PI use than those on INSTIs, and 1.58 (-0.94, 4.11) m/s higher than those on NNRTIs, although these differences were not significant. Conclusions: PWV was within normal ranges in most YPHIV and YPHEU although 5% YPHIV had elevated PWV. PWV may be higher with PI use due to cardiometabolic side effects. Successful HIV treatment and control of traditional CV risk factors may prevent premature vascular aging and subsequent cardiac compromise in YPHIV.

Abstract Su706: New risk markers of sudden cardiac death in the young : insights from machine learning on EHR data

Background: Sudden Cardiac Death (SCD) in young adults is a significant public health issue, with survival rates often less than 15%. Effective prevention is critical as many SCD cases go undetected due to nonspecific symptoms and ineffective risk stratification methods, especially among the youth. Objective: To explore risk markers specific to SCD in younger populations using Artificial Intelligence (AI) trained on systematically collected Electronic Health Records (EHR) data, and to compare these markers with those in older populations. Methods: We conducted a retrospective cohort study using data from 46,060 participants in Paris and its inner suburbs, spanning 2011 to 2020. The cohort included 1,100 SCD cases and 1,100 controls aged 40 years or younger, and 21,930 SCD cases and 21,930 controls aged over 40. A machine learning model was developed, trained, and validated on these cohorts. We used the Catboost algorithm and evaluated model performance using AUC, sensitivity, and specificity. The SHAP algorithm was employed to elucidate the relationship between variables and predicted risk. Results: The model achieved on validation sets an AUC of 0.75 (95% CI 0.67-0.83) for the younger cohort and AUC of 0.82 (95% CI: 0.70-0.83), for the older cohort. Neuropsychiatric drugs were the most influential predictors for the younger cohort, whereas age and cardiovascular drugs were most predictive for the older cohort. The results indicate that traditional cardiovascular risk factors play a secondary role in predicting SCD among younger individuals. Conclusion: In analyzing predictors of sudden death in individuals under 40, we developed a personalized SCD prediction model using EHR data tailored to this demographic. Psychiatric medications, and possibly underlying psychiatric conditions, emerged as significant predictors. Our findings emphasize the need for a multidisciplinary approach to SCD prevention, integrating neuropsychiatric and cardiovascular considerations.

Abstract 4137939: Mosaic loss of Y chromosome is associated with increased all-cause mortality in patients with ST-segment elevation myocardial infarction

Introduction: Mosaic loss of Y chromosome (LOY), a common subtype of somatic mosaicism, is characterized as loss of the entire Y chromosome in a mosaic manner and increases with age. Accumulating evidence has manifested the positive link between LOY and shorter life expectations in elderly men as well as common age-associated diseases, such as cancer and cardiovascular diseases. Experimental studies also demonstrated that hematopoietic LOY in mice induced cardiac fibrosis and led to increased mortality. However, little is known about LOY and prognosis of ST-segment elevation myocardial infarction (STEMI). Hypothesis: We hypothesized that LOY may be associated with lower survival rate of patients with STEMI. Aims: Investigating the impact of LOY in peripheral blood cells on prognosis of patients with STEMI. Methods: This study prospectively enrolled 928 males and 272 females undergoing primary percutaneous coronary intervention for STEMI. LOY was measured in 928 males using droplet digital polymerase chain reaction technique. Results: During a median follow-up of 3.99 years, 93 males (10.0%) and 45 females (16.5%) died. After adjusting for traditional cardiovascular risk factors, the risk of all-cause mortality in males with LOY ≥ 18% (the 90th percentile of LOY) increased to 2.45 (95% confidence intervals [CI]: 1.16–5.15, P = 0.018), 2.11 (95% CI: 1.11–4.01, P = 0.024), and 1.88 (95% CI: 1.02–3.45, P = 0.043) times during 1-, 2-, and 3-year follow-up, respectively, compared to males with LOY < 18%. Among males without prior MI, those with LOY ≥ 18% had an increased risk of all-cause mortality compared to those with LOY < 18% (adjusted hazard ratio 1.93, 95% CI: 1.01–3.67; P = 0.045); this was not observed for males with prior MI. Female patients had a 1.71-fold (95%CI: 1.04–2.81; P = 0.035) increased risk of all-cause mortality than males with LOY < 18%, whereas the risk was similar to males with LOY ≥ 18%. Conclusion: LOY was associated with an increased risk of all-cause mortality in male STEMI patients, particularly in those without prior MI. Detecting LOY in STEMI patients could help further refine sex differences in prognosis and assist in identifying male patients with better prognoses.

Sex Differences in Cardiovascular Risk Profiles of Patients with Rheumatoid Arthritis: Results from an Italian Multicentre Cohort

Objective: The effect of sex and gender-related variables on the evaluation of cardiovascular (CV) risk in rheumatoid arthritis patients has been poorly explored. We investigated the differences in CV risk features and scores according to sex in a wide rheumatoid arthritis (RA) cohort. Methods: This is a cross-sectional analysis of a consecutive RA cohort. Disease-specific clinical and serologic variables, traditional CV risk factors and the 10-year CV risk calculated by the SCORE-2, Progetto CUORE and Expanded Risk Score-RA algorithms were compared in males and females. Results: A total of 820 patients (193 men, 627 women) were included. Disease activity was similar between the two sexes. A significantly higher prevalence of traditional CV risk factors and higher mean CV risk scores were detected in male compared to female patients. In the multiple linear regression analysis, a higher HAQ, csDMARD use and ACPA positivity were significantly associated with an increased CV risk in females, while b/tsDMARDs was associated with a lower CV risk in males according to different algorithms. Conclusions: The distribution of traditional CV risk factors and the 10-year risk of CV disease significantly differed in female and male patients despite similar disease activity. Disease-specific variables may contribute differently to CV risk according to sex. The CV screening in RA should also take into account the different distribution of CV risk factors between sexes.

Adherence to the 2019 ESC/EAS guidelines for dyslipidaemia management in a large rheumatoid arthritis cohort: Data from the CORDIS Study Group of the Italian Society of Rheumatology

Background/aimLipid-lowering therapy prescription is low in rheumatoid arthritis (RA) patients, often not achieving lipid threshold target despite treatment. However, evidence derives from small, monocentric cohorts. We assessed adherence to lipid-lowering treatment for primary cardiovascular (CV) prevention in a RA cohort according to international guidelines. MethodsA cross-sectional analysis of an Italian RA cohort was performed. Disease-related features and traditional CV risk factors were collected. The 10-year CV risk was estimated by Systematic COronary Risk Evaluation 2 (SCORE-2) algorithm. The primary preventive dyslipidaemia strategy was assessed according to 2019 European Society of Cardiology/European Atherosclerosis Society guidelines. Results1.133 RA patients (78.2% female, aged 60.6±10.2 years) free from CV events were included. According to SCORE-2, 42.9% of patients were at moderate risk (1–5-%), 33.3% at high risk (5–10%) and 23.7% at very high risk (>10%). In the whole cohort, 12.9% of patients with <5%, 23.6% with 5–10% and 32.3% with >10% risk were on statin, respectively (p<0.001). According to 2019 ESC/EAS guidelines, 51.5% of patients had LDL-c at target. Among patients with LDL-c not at target, 76% were not on lipid-lowering treatment. At multivariate analysis, patients with higher CV risk had significantly lower probability of LDL-c at target. ConclusionIn a wide Italian RA cohort, more than 50% of patients had high or very high CV risk. In these, lipid-lowering treatment prescription is suboptimal leading to not achievement of LDL-c target. Physicians should improve lipid screening and primary prevention therapy to reduce CV risk and improve CV comorbidity in RA patients.

Coronary Artery Vasculitis and Encasement: Multimodality Imaging Findings and Mimics.

Coronary artery vasculitis (CAV) and coronary artery encasement are rarely diagnosed conditions that are important diagnostic considerations, particularly in patients with acute coronary syndrome without traditional cardiovascular risk factors or systemic illness. Vasculitis refers to inflammation of the blood vessel walls, which can be primary or secondary. This process should be distinguished from neoplastic involvement of the coronary arteries, termed coronary artery encasement. Prospective diagnosis of these diseases is challenging, often requiring multidisciplinary workup with careful attention to clinical presentation and multiorgan findings. While CAV and coronary artery encasement can be indistinguishable at coronary CT angiography, certain imaging features help order the differential diagnosis. CAV should be considered when there is smooth wall thickening that is circumferential and/or continuous. A diagnosis of coronary artery encasement is favored when there is irregular or nodular wall thickening that is eccentric to the vessel lumen. Epicardial fat stranding may also appear more extensive compared with CAV. Potential mimics of CAV include atherosclerosis, acute plaque rupture, coronary artery aneurysm, and spontaneous coronary artery dissection. Detection and diagnosis of CAV may help avoid complications related to accelerated atherosclerosis and infarction. Radiologists should be familiar with the range of pathologic conditions that can affect the coronary arteries beyond atherosclerosis as they may be the first to raise such diagnostic possibilities, guiding next steps in patient workup and management. ©RSNA, 2024 Supplemental material is available for this article.

Correlation of Sarcopenia with Coronary Artery Disease Severity and Pericoronary Adipose Tissue Attenuation: A Coronary CT Study

Objective: To investigate the association between sarcopenia, as appraised with CT-derived muscle metrics, and cardiovascular status, as assessed via coronary CT angiography (CCTA) using the Coronary Artery Disease-Reporting and Data System (CAD-RADS) and with pericoronary adipose tissue (pCAT) metrics. Methods: A retrospective observational study conducted on patients who underwent CCTA. The cross-sectional area (CSA) and attenuation values of the paravertebral muscles at the T8 level and the pectoralis major muscles at the T6 level were measured. The patient height was employed for the normalization of the skeletal muscle CSA. The pCAT attenuation around the coronary arteries was assessed, and the CAD severity was graded using the CAD-RADS reporting system. Regression analyses were performed to assess the impact of demographics, clinical factors, and CT variables on the CAD-RADS and pCAT. Results: A total of 220 patients were included (132 males, median age 65 years). Regression analyses showed the associations of CAD with age and sex (p &lt; 0.001). Familiarity with CAD was related to the left anterior descending artery pCAT (p = 0.002) and circumflex artery pCAT (p = 0.018), whereas age was related to the left anterior descending artery pCAT (p = 0.032). Weak positive correlations were found between the lower muscle density and lower pCAT attenuation (ρ = 0.144–0.240, p &lt; 0.039). Conclusions: This study demonstrated weak associations between the sarcopenia indicators and the cardiovascular risk, as assessed by the CAD severity and pCAT inflammation. However, these correlations were not strong predictors of CAD severity, as age and traditional cardiovascular risk factors overshadowed the impact of sarcopenia in the cardiovascular risk assessment.

Prognostic role of remnant cholesterol and traditional cardiovascular risk factors in young adults: results of long-term follow-up of a cohort of 30-year-old norwegians

Abstract Background There are limited data on the prevalence and impact of traditional cardiovascular (CV) risk factors among young adults. In addition, more knowledge on novel CV risk factors is needed to explain the residual risk beyond that of the traditional risk factors. Increasing evidence suggest a causal role of remnant cholesterol (RC) in the development of atherosclerotic cardiovascular disease (CVD) and subsequent clinical events. However, the role of RC in young adults is unresolved. Purpose We aimed to evaluate the prevalence of traditional risk factors and the respective sex-differences in young adults, as well as their association with long-term CV events. Further, we hypothesized that higher RC concentrations are associated with impaired CV prognosis. Methods In year 2000, all 30-year-old inhabitants of our city were invited to a cross-sectional study including assessment of health status, anthropometric measurements, and non-fasting blood samples. RC was calculated as total cholesterol minus (LDL-C + HDL-C). Long-term clinical follow-up was performed through linkage with mandatory national registries, 22 years after inclusion. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for unstable angina and coronary revascularization. Results A total of 5950 individuals were included (56% women). At baseline, men displayed significantly higher systolic and diastolic blood pressure, total cholesterol, LDL-C and triglycerides, as compared with women (Table 1). Also, men had higher levels of RC (Table 1). During a mean follow-up time of 22 years, 108 events (1.8%) occurred. In multivariable Cox regression analysis, non-West-European ancestry (adjusted [a] HR 1.76, 95% confidence interval [CI] 1.03-2.99), diabetes mellitus (aHR 6.39, 95% CI 2.52-16.2), systolic blood pressure (aHR 1.03, 95% CI 1.01-1.04), and LDL-cholesterol (aHR 1.37, 95% CI 1.11-1.68) were associated with an increased risk of CV events during long-term follow-up. Female gender was associated with a reduced risk of CV events (aHR 0.38, 95% CI 0.23-0.64), whereas smoking status did not show any significant association. RC was identified as a significant predictor of CV events (aHR 1.55, 95% CI 1.11-2.18, per 1.0 mmol/L increase). The highest RC quartile (mean RC: 1.1 mmol/L), had the highest event rate (Figure 1, p&amp;lt;0.001 with log-rank test). Conclusion This study uncovers significant sex-differences in modifiable CV risk factors among young adults at the age of 30, which are associated with increased risk for long-term CV events. Interestingly, increasing concentrations of RC at the age of 30 were strongly associated with impaired long-term CV outcome and should be accounted for in early risk prediction.Baseline characteristics.Remnant cholesterol and CVD events.

Traditional cardiovascular risk factors and coronary microvascular disease in women and men- a single center study

Abstract Introduction Coronary microvascular dysfunction (CMD) is a common, often missed, cause for effort intolerance and angina symptoms, and is associated with adverse clinical outcomes. Risk factors for the development of CMD have not been fully elucidated, and studies examining sex associated differences in traditional cardiovascular risk factors (TCRs) for obstructive coronary artery disease (CAD) in patients with CMD have yielded conflicting results. Although several non-invasive methods for the evaluation of CMD exist, currently, catheter-based invasive assessment is the gold standard for the diagnosis of coronary microvascular dysfunction. Purpose To examine the association between TCR and CMD and sex associated differences in TCR, in a prospective cohort of patients undergoing invasive microvascular function evaluation in a large tertiary medical center. Methods In this single center, prospective registry, we enrolled patients with non-obstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Measurements of microvascular function included CFR, IMR, RRR as well as FFR. Pathologic CFR was defined as &amp;lt;2.5 or &amp;lt;2. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. Results Overall, 245 patients with non-obstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range [IQR]: 59,75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men in the entire cohort (59.0% vs. 57.0%; p=0.77). In 41 patients diagnosed with functional microvascular dysfunction there were more women than men (70.7% vs. 29%). When using a threshold of CFR&amp;lt;2.5 no association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (CFR) (β=-0.29; p&amp;lt;0.01 and β=-0.15; p=0.05, respectively) and lower resistive reserve ratio (RRR) (β=-0.28; p&amp;lt;0.01 and β=-0.17; p=0.04, respectively). When using a threshold of &amp;lt;2.0 for CFR similar results were found. Conclusion The prevalence of TCRs was similar in patients with and without CMD. In women, older age and previous IHD were associated with lower CFR and RRR values while no association between TCRs and indices of CMD was found in men. It is likely that there are other, currently unknown risk factors for CMD as well as unique risk factors for each of its endotypes, beyond TCRs. It is unclear which parameter of microvascular dysfunction is the most accurate, and whether different parameters should be used in women and men. Large-scale multi-center studies to further evaluate these issues are needed.Variables associated with CMDStudy inclusion process

Endothelial dysfunction in acute coronary syndrome: a complex association with cardiovascular risk factors, sleep quality and cardiorespiratory capacity

Abstract Introduction It is widely acknowledged that normal endothelial function plays a pivotal role in conferring cardioprotective effects against ischemia-reperfusion injury following acute myocardial infarction (AMI) treated by a primary percutaneous coronary intervention (PCI), thereby limiting infarct size (1). However, endothelial dysfunction (ED) has been extensively documented in patients with cardiovascular (CV) risk factors (2). This study proposes a novel perspective, positing that ED could be intricately linked not only with traditional CV risk factors, but also it can be associated with poor sleep quality. Consequently, this interplay might significantly contribute to the attenuation of exercise capacity. Objective The aim of this study was to assess endothelial function following AMI treated with a PCI and investigate the link between endothelial function, CV risk factors, sleep quality and exercise capacity. Furthermore, the study aimed to determine if endothelial function could serve as a predictive factor for future major adverse acute cardiac events (MAACE) following AMI. Materials and methods Sixty-three patients with AMI (56.21 ± 7.6 years) volunteered to participate in this study, . Endothelial function was assessed using the Endothelium Quality Index (EQI) . Sleep quality was evaluated using both actigraphy and the PSQI (Pittsburgh Sleep Quality Index) questionnaire. Exercise capacity was quantified through the 6-minute walking test (6mwt). Results ED was evident, as indicated by an EQI of 1.4 ± 0.7. Furthermore, ED was notably influenced by CV risk factors such as low physical activity level, age, and smoking. A significant correlation was found between EQI and both sleep efficiency (r = 0.340; p = 0.006) and PSQI score (r = -0.533; p &amp;lt; 0.001). Additionally, a strong association was observed between endothelial function and the results of the 6mwt (r = 0.291; p = 0.021). Furthermore, during a follow up period ( near 4 months) following PCI, MAACE were observed in patients with severe ED only. Conclusion In summary, findings of this study may emphasize the importance of enhancing sleep quality and advocating for an active lifestyle as modifiable elements to enhance endothelial function, which can be regarded as a prognostic tool subsequent to AMI, ultimately contributing to improved clinical outcomes. Moreover, this study concluded that AMI patients with severe endothelial dysfunction were more likely to develop MAACE.Endothelial Dysfunction after AMIED following AMI : Causes and effect

Pericoronary adipose tissue computed tomography attenuation (PCAT) as a marker of premature CVD in asymptomatic people living with HIV (PLWH) without traditional risk factors: H-ART to heart study

Abstract Background Controversy exists regarding the contribution of HIV, ART or traditional risk factors to CVD risk in PLWH. The H-ART to Heart study investigates the prevalence of subclinical CVD in asymptomatic PLWH without cardiovascular risk factors compared to negative controls(-). Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and thus can be detected on coronary computed tomography angiography (CTCA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). Methods This cross-sectional study compared PLWH aged 35-55yrs (diagnosed &amp;gt;10 yrs, on ART) to matched controls. Included were Caucasian men who have sex with men(MSM) and Black African/Caribbean women (BW) with traditional risk factors excluded (hypertension, hyperlipidaemia, diabetes, kidney disease, smoking, depression, inflammatory conditions, etc.). Detailed vitals, 10 year CVD risk calculation (Q-RISK 3) were recorded. CTCA were performed with novel analysis using PCAT to assess for coronary inflammation (Figure 1.) Results 98 participants were recruited (49M; 51 PLWH). Mean Q Risk 3 (10yr CVD risk - %) was low across the groups (HIV+MSM 4.65±2.1, HIV-MSM 3.88±2.7;p=0.29; HIV+BW 2.03±1.3, HIV-BW 1.38±0.98 p=0.66). 79 participants (42 PLWH; 37 controls) completed a CTCA with only 2 PLWH having clinically significant disease (CAD-RAD 3+ ie. &amp;gt;50% luminal stenosis) and none in the control group. (p=0.49) The CT scans of 69 patients were assessed for peri-coronary adipose tissue (PCAT) density, 2 were ruled out due to a small non-dominant RCA. The PCAT density of PLWH was higher than that of the controls (-71.2±27.6 vs -75.5±30.3 P=&amp;lt;0.05). Multivariate linear regression demonstrated that HIV status was an independent predictor of coronary inflammation (p=0.037) after adjusting for age, gender and BMI. Conclusion PWLH without traditional CV risk factors did not have significant evidence of more clinically relevant stenosis than controls on CTCA. However PCAT demonstrated a higher signal of coronary inflammation, despite stable disease, compliance with ART and low CVD risk scores. PLWH remain at risk of CV disease, this study supports the rationale for early preventative strategies for CVD prevention in PLWH.PCAT showing HIV inflammation Vs Control

Risk of recurrent ischaemic events in ACS patients with baseline LDL-C below guideline-recommended thresholds: insights from the prospective SPUM-ACS study

Abstract Introduction The 2023 European Society of Cardiology (ESC) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with acute coronary syndromes (ACS), adding ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to achieve recommended target goals (LDL-C&amp;lt;55 mg/dL). Purpose This population-based, real-world study aimed to examine cardiovascular (CV) events in ACS patients with baseline LDL-C levels below current guideline thresholds. Methods ACS patients admitted to four Swiss University Hospitals and enrolled in the multicenter SPUM registry (NCT 01000701) between 2009 and 2017 were followed prospectively until 1 year. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE); i.e., non-fatal stroke, myocardial infarction (MI), and death) at 1 year. Multivariable-adjusted Cox proportional hazard regression models were fit to estimate ischaemic risk among those with LDL-C&amp;lt;55 mg/dL. Results Out of 4’787 ACS patients, 226 patients (4.7%) had baseline LDL-C&amp;lt;55 mg/dL. These patients were older (69.7±11.3 vs 63.4±12.4, p&amp;lt;0.001), more frequently male (20.8%vs 15.9%, p&amp;lt;0.001), had more often traditional CV risk factors (all p&amp;lt;0.001) and were more likely to have a complex history of CV disease, such as previous MI (37.2% vs 10.9%, p&amp;lt;0.001), prior percutaneous (47.8% vs 13.2%, p&amp;lt;0.001) or surgical (15.0% vs 3.5%, p&amp;lt;0.001) coronary revascularization. Inflammatory biomarkers were also higher (hs-CRP, 30.1±63.6 vs 10.7±25.8 mg/L), with most patients being on high-dose statin therapy (82.4% vs 38.7%, p&amp;lt;0.001). At 1 year, patients with LDL-C&amp;lt;55 mg/dL had a higher rate of MACCE (16.4% vs 7.0%, p&amp;lt;0.001), with individual components of the primary endpoint occurring more frequently among these patients (all p&amp;lt;0.001), except for a numerical increase in CE (2.7% vs 1.7%, p=n.s.), as shown in the figure (Panel A). The enhanced MACCE risk persisted after adjustment for potential differences in baseline characteristics, with a 51% (adj. HR 1.51, CI95% 1.05-2.17, p=0.026) increase in MACCE (Panel B). Diabetes, low eGFR and high hs-CRP levels remained independent predictors of MACCE in patients with low baseline LDL-C (all p&amp;lt;0.001). Conclusions Our real-world data confirm that even ACS-patients reaching currently recommended LDL-C thresholds have a substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to further reduce CV risk.Event-risk according to baseline LDL-C