Traditional CVD Risk Factors Research Articles

The association of inflammation, triglycerides and lipoprotein(a) with cardiovascular events in the UK Biobank

Abstract Background Recent trial data has suggested that high-sensitivity C-reactive protein (hsCRP) is, at least, as strong a predictor of future cardiovascular events as LDL cholesterol in patients on lipid-lowering therapy1,2. There are limited data however on how hsCRP and other additional risk factors perform in patients at different levels of CVD risk. Purpose To evaluate the relationship of hsCRP, triglyceride and lipoprotein(a) [Lp(a)] levels with cardiovascular events in guideline-defined, clinically distinct cohorts. Such a study will improve the understanding of CVD risk prediction and provide essential information on the role of these pathways in CVD. Methods Data from the UK Biobank were used. In accordance with the 2021 ESC CVD prevention guidelines, four risk groups were derived based on clinical data and 10-year CVD risk, calculated from the recently derived SCORE2 model (Figure 1)3. Those not falling into one of the four cohorts were excluded as further risk stratification in these individuals would not influence management. For increasing quartiles (Q) of each biomarker, hazard ratios (HR), 95% confidence intervals (CI) and p-values were calculated relative to the lowest Q, using Cox proportional hazards models, adjusted for age, sex, smoking status, systolic blood pressure, HDL cholesterol and total cholesterol. Interactions between sex and biomarker were explored. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, and ischaemic stroke. Secondary endpoints were the individual components of the primary endpoint. Results A total of 229,339 participants were included across the four risk groups, with a total of 24,133 primary endpoint events over the mean follow-up period of 14 years. In all four groups there was a robust linear relationship of hsCRP with MACE (p<0.001 [Figure2]) – strongest in the secondary prevention population (Q4 v Q1 HR=1.79 [95%CI:1.60, 2.02]). Of the secondary endpoints, hsCRP was most strongly associated with cardiovascular death (Q4 v Q1 secondary prevention cohort HR=1.97 [1.68, 2.30]). Lp(a) was associated with MACE in the primary prevention cohorts only (Q4 vs Q1 high-risk cohort HR=1.35 [1.27, 1.44]), driven by its strong association with myocardial infarction (Q4 vs Q1 HR 1.61 [1.48, 1.75]) but not other secondary endpoints. After adjustment, triglyceride levels were not associated with MACE in the four cohorts. There was no evidence of sex interactions in any analysis (p>0.05). Conclusions After adjustment for traditional CVD risk factors, hsCRP is a more robust predictor of cardiovascular events than Lp(a) or triglycerides in both primary and secondary prevention settings. Consideration should be given to evaluating whether hsCRP, Lp(a) and other ‘non-traditional’ risk factors can improve CVD risk reclassification and/or be used to guide allocation to targeted anti-atherosclerotic therapies.Figure 1:Participant FlowFigure 2:Main effects

Genetic risk score for coronary artery calcification and its predictive ability for coronary artery disease

AimThe modest added predictive value of the existing genetic risk scores (GRSs) for coronary artery disease (CAD) could be partly due to missing genetic components, hidden in the genetic architecture of intermediate phenotypes such as coronary artery calcification (CAC). In this study, we investigated the predictive ability of CAC GRS for CAD. Materials and methodsWe investigated the association of CAC GRSs with CAD and coronary calcification among the participants in the Ludwigshafen Risk and Cardiovascular Health study (LURIC) (n = 2742), the Tampere Vascular Study (TVS) (n = 133), and the Tampere Sudden Death Study (TSDS) (n = 660) using summary data from the largest multi-ancestry GWAS meta-analysis of CAC to date. Added predictive value of the CAC GRS over the traditional CVD risk factors as well as metaGRS, a GRS for CAD constructed with 1.7 million genetic variants, was tested with standard train–test machine learning approach using the LURIC data, which had the largest sample size. ResultsCAC GRS was significantly associated with CAD in LURIC (OR=1.41, 95 % CI [1.28–1.55]), TVS (OR=1.79, 95 % CI [1.05–3.21]) as well as in TSDS (OR=4.20, 95 % CI [1.74–10.52]). CAC GRS showed strong association with calcification areas in left (OR=1.78, 95 % CI [1.16–2.74]) and right (OR=1.71, 95 % CI [1.98–2.67]) coronary arteries. There was statistically significant added predictive value of the CAC GRS for CAD over the used traditional CVD risk factors (AUC 0.734 vs 0.717, p-value = 0.02). Furthermore, CAC GRS improved the prediction accuracy for CAD when combined with metaGRS. ConclusionsThis study showed that CAC GRS is a new risk marker for CAD in three European cohorts, with added predictive value over the traditional CVD risk factors.

Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.

Preeclampsia, a pregnancy disorder characterized by de novo hypertension and maternal multisystem organ dysfunction, is the leading cause of maternal mortality worldwide and is associated with a fourfold greater risk of cardiovascular disease throughout the lifespan. Current understanding of the etiology of preeclampsia remains unclear, due in part to the varying phenotypical presentations of the disease, which has hindered the development of effective and mechanism-specific treatment or prevention strategies both during and after the affected pregnancy. These maternal sequelae of preeclampsia are symptoms of systemic vascular dysfunction in the maternal nonreproductive microvascular beds that drives the development and progression of adverse cardiovascular outcomes during preeclampsia. Despite normalization of vascular disturbances after delivery, subclinical dysfunction persists in the nonreproductive microvascular beds, contributing to an increased lifetime risk of cardiovascular and metabolic diseases and all-cause mortality. Given that women with a history of preeclampsia demonstrate vascular dysfunction despite an absence of traditional CVD risk factors, an understanding of the underlying mechanisms of microvascular dysfunction during and after preeclampsia is essential to identify potential therapeutic avenues to mitigate or reverse the development of overt disease. This article aims to provide a summary of the existing literature on the pathophysiology of maternal microvascular dysfunction during preeclampsia, the mechanisms underlying the residual dysfunction that remains after delivery, and current and potential treatments both during and after the affected pregnancy that may reduce microvascular dysfunction in these high-risk women. © 2024 American Physiological Society. Compr Physiol 14:5703-5727, 2024.

Cardiovascular risk in US adults with nonalcoholic steatohepatitis (NASH) vs. matched non-NASH controls, National Health and Nutrition Examination Survey, 2017-2020.

NASH is considered a contributor to atherosclerotic cardiovascular disease (ASCVD) risk; however, its contribution beyond traditional risk factors for CVD, particularly diabetes, is less clearly understood. This study aimed to quantify the cardiovascular-event risk associated with NASH, independent of diabetes status. A cross-sectional analysis was conducted using the 2017-2020 NHANES pre-pandemic cycle. NASH was defined based on presence of steatosis without other causes of liver disease, and FibroScan+AST score from vibration-controlled transient elastography (VCTE). Significant fibrosis (stages F2-F4) was identified by liver stiffness measurement from VCTE. Predicted primary CV-event risk was estimated using both the Pooled Cohort Equations (PCE) and the Framingham Risk Score (FRS). NASH patients were matched with non-NASH controls on age, sex, race/ethnicity, and diabetes status. Weighted logistic regression was conducted, modeling elevated predicted CV risk (binary) as the dependent variable and indicators for NASH / fibrosis stages as independent variables. A sample of 125 NASH patients was matched with 2585 controls. NASH with significant fibrosis was associated with elevated predicted 10-year CV risk, although this association was only statistically significant in PCE analyses (odds ratio and 95% CI 2.34 [1.25, 4.36]). Analyses restricting to ages <65 years showed similar results, with associations of greater magnitude. Independent of diabetes, a significant association was observed between NASH with significant liver fibrosis and predicted primary CV-event risk in US adults, particularly for those <65. These findings suggest the importance of accounting for NASH and liver-fibrosis stage in predicting CV-event risk.

APOL1 polymorphisms are not influencing acute coronary syndrome risk in Czech males.

The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow-up. We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.

Unraveling Changes of Brachial Artery Residual Stress and Its Relationship to Cardiovascular Disease Risk Factors.

Arterial pressure volume index (API) offers a non-invasive measurement of brachial artery residual stress. This study investigated API distribution characteristics and correlations with cardiovascular disease risk (CVD) factors in a large Chinese population sample. This cross-sectional study surveyed a total of 7620 participants. We analyzed the relationships between API and factors influencing CVD, using regression-based stepwise backward selection and restrictive cubic spline models to express relationships as standardized beta values. Multiple linear regression analysis identified many independent factors influencing API including age, sex, body mass index (BMI), pulse pressure (PP), heart rate (HR), hemoglobin, uric acid (UA), estimated glomerular filtration rate (eGFR), triglyceride (TC), and a history of hypertension. Notably, API values increased at 33 and escalated with advancing age. Increases in API were associated with rises in PP and UA increases, particularly when PP reached 60 mmHg and the UA reached 525 units. Conversely, API was found to decrease with elevated HR and eGFR. Furthermore, there was a significant inverted U-shaped relationship between API and BMI. This study was the first to describe API distribution characteristics in a large sample of the Chinese population, providing references for evaluating API changes in the assessment of residual stress variations in diverse diseases. Notably, API displayed a U-shaped relationship with age and was closely related to traditional CVD risk factors, underscoring its potential as a non-invasive tool for risk assessment in vascular health. This research was registered with the China Clinical Trial Registration Center (Registration Number: ChiCTR2000035937).

Risk factor profile and outcomes in young patients presenting with acute ST-segment elevation myocardial Infarction

Abstract Introduction ST-elevation myocardial infarction (STEMI) is more prevalent in the elderly population1, but is now becoming more common in the younger population. It has been of particular concern due to its potential for premature death and long-term morbidity. Early identification and timely modification of risk factors in this population is critical2,3. Secondary prevention issues in populations are well studied, and such data for young adults are lacking in the literature. Purpose The purpose of this study was to compare pattern of traditional CVD risk factors, hospital mortality and major adverse cardiac events at discharge in young versus old patients (≤45years and above 45 years age respectively) admitted with STEMI and undergoing primary PCI. Methods This retrospective cohort study was conducted on consecutive patients presenting with STEMI between June 2013 and June 2018 in a single centre cardiac only tertiary care setup. Institute’s registry is fashioned along and is affiliated with US NCDR. Patients with cardiac arrest or cardiogenic shock at arrival were excluded. MACE was defined as post PCI cardiac arrest or cardiogenic shock, heart failure, major bleed or hospital death. Results Total of 5343 patients were admitted with STEMI during study period, after exclusion data of 1642 patients were analyzed. Table 1 demonstrates demographic and historical characteristics of the study population. Among young patients, the frequency of the male gender,any tobacco use and family history of premature coronary artery disease were significantly higher (all p values &amp;lt; 0.001). While in older STEMI patients frequency of heart failure, hypertension, prior myocardial infarction, diabetes mellitus ,abnormal creatinine clearance (&amp;lt;90 mL/min/1.73 m²) , multi-vessel coronary disease, advanced Killip class and higher body mass index was more prevalent (all P&amp;lt;0.001). Table 2 demonstrates predictors of in hospital death and MACE. Among young patients advanced Killip class and femoral access site(all P values &amp;lt;0.001), diabetes mellitus (p=0.03), abnormal creatinine clearance(p=0.04),and left ventricular ejection fraction less than 40%(p=0.01), were more significant in-hospital mortality predictor where as advanced Killip class,Left ventricular ejection fraction less than 40% male gender(p=0.04), diabetes mellitus(p=0.001),femoral access site(p=0.001), and Left ventricular ejection fraction less than 40% were more significant MACE predictors (all P&amp;lt;0.001). Conclusion There were no significant difference in hospital mortality and MACE among young versus old STEMI patients when adjusted for diabetes mellitus, abnormal creatinine clearance (&amp;lt;90 mL/min/1.73 m²), multi-vessel coronary disease, advanced Killip class. Tobacco use is the main modifiable risk factors for young patients with STEMI. Surprisingly, being a woman and having a positive family history with premature coronary artery disease were protective.

Personalizing cardiovascular risk prediction for patients with systemic lupus erythematosus

ObjectiveCardiovascular disease (CVD) risk is increased in SLE and underestimated by general population prediction algorithms. We aimed to develop a novel SLE-specific prediction tool, SLECRISK, to provide a more accurate estimate of CVD risk in SLE. MethodsWe studied patients in the Brigham and Women's Hospital SLE cohort. We collected one-year baseline data including the presence of traditional CVD factors and SLE-related features at cohort enrollment. Ten-year follow-up for the first major adverse cardiovascular event (MACE; myocardial infarction (MI), stroke, or cardiac death) began at day +1 following the baseline period (index date). ICD-9/10 codes identified MACE were adjudicated by board-certified cardiologists. Least absolute shrinkage and selection operator regression selected SLE-related variables to add to the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equations 10-year risk Cox regression model. Model fit statistics and performance (sensitivity, specificity, positive/negative predictive value, c-statistic) for predicting moderate/high 10-year risk (≥7.5 %) of MACE were assessed and compared to ACC/AHA, Framingham risk score (FRS), and modified FRS (mFRS). Optimism adjustment internal validation was performed using bootstrapping. ResultsWe included 1,243 patients with 90 MACEs (46 MIs, 36 strokes, 19 cardiac deaths) over 8946.5 person-years of follow-up. SLE variables selected for the new prediction algorithm (SLECRISK) were SLE activity (remission/mild vs. moderate/severe), disease duration (years), creatinine (mg/dL), anti-dsDNA, anti-RNP, lupus anticoagulant, anti-Ro positivity, and low C4. The sensitivity for detecting moderate/high-risk (≥7.5 %) of MACE using SLECRISK was 0.74 (95 %CI: 0.65, 0.83), which was better than the sensitivity of the ACC/AHA model (0.38 (95 %CI: 0.28, 0.48)). It also identified 3.4-fold more moderate/high-risk patients than the ACC/AHA. Patients who were moderate/high-risk according to SLECRISK but not ACC/AHA, were more likely to be young women with severe SLE and few other traditional CVD risk factors. Model performance between SLECRISK, FRS, and mFRS were similar. ConclusionThe novel SLECRISK tool is more sensitive than the ACC/AHA for predicting moderate/high 10-year risk for MACE and may be particularly useful in predicting risk for young females with severe SLE. Future external validation studies utilizing cohorts with more severe SLE are needed.

Risk Factor Profile and Hospital Outcomes in Patients ≤ 45 Years vs. &gt;45 Years of Age Presenting with Acute ST-Segment Elevation Myocardial Infarction

Objectives: In Pakistan, cardiovascular risk factors for acute myocardial infarction are increasing. There are few studies available on atherosclerotic risk factors in young patients and its outcome The purpose of this study was to compare pattern of traditional CVD risk factors, hospital mortality and major adverse cardiac events at discharge in young versus old patients (≤45years and above 45 years age respectively) admitted with STEMI and undergoing primary PCI.&#x0D; Methodology: This retrospective cohort study was conducted on consecutive patients presenting with STEMI between June 2013 and June 2018 in a single centre cardiac only tertiary care setup. Institute’s registry is fashioned along and is affiliated with US NCDR. Patients with cardiac arrest or cardiogenic shock at arrival were excluded. MACE was defined as post PCI cardiac arrest or cardiogenic shock, heart failure, major bleed or hospital death. Models were built using stepwise forward logistic regression method.&#x0D; Results: Total of 5343 patients were admitted with STEMI during study period, after exclusion data of 1642 patients were analyzed. Among young patients, the frequency of the male gender, any tobacco use and family history of premature coronary artery disease were significantly higher (all p values &lt; 0.001). While in older STEMI patients frequency of heart failure, hypertension, prior myocardial infarction, diabetes mellitus ,abnormal creatinine clearance (&lt;90 mL/min/1.73 m²) , multi-vessel coronary disease, advanced Killip class and higher body mass index was more prevalent (all P&lt;0.001). Among young patients advanced Killip class and femoral access site(all P values &lt;0.001), diabetes mellitus (p=0.03), abnormal creatinine clearance(p=0.04),and left ventricular ejection fraction less than 40%(p=0.01), were more significant in-hospital mortality predictor whereas advanced Killip class, Left ventricular ejection fraction less than 40% male gender(p=0.04), diabetes mellitus(p=0.001),femoral access site(p=0.001), and Left ventricular ejection fraction less than 40% were more significant MACE predictors (all P&lt;0.001).&#x0D; Conclusion: There were no significant difference in hospital mortality and MACE among young versus old STEMI patients when adjusted for diabetes mellitus, abnormal creatinine clearance (&lt;90 mL/min/1.73 m²), multi-vessel coronary disease, advanced Killip class. Tobacco use is the main modifiable risk factors for young patients with STEMI. Surprisingly, being a woman and having a positive family history with premature coronary artery disease were protective.

Abstract 13721: Coronary Artery Calcium for Risk Stratification Among Persons With Very-High High-Density Lipoprotein Cholesterol

Introduction: Persons with very-high high-density lipoprotein-cholesterol (HDL-C) may experience an increased mortality risk. However, the predictors of mortality among those with very-high HDL-C remain unknown. Hypothesis: Compared to traditional risk factors, coronary artery calcium (CAC) will more strongly stratify risk among individuals with very-high HDL-C. Aims: Among individuals with very-high HDL-C, to 1) calculate crude all-cause mortality rates across the burden of traditional risk factors and CAC, and 2) identify independent risk factors associated with all-cause mortality. Methods: There were 335 primary prevention patients from the CAC Consortium who had very-high HDL-C ( &gt; 80 mg/dL in men, &gt; 100 mg/dL in women) and available information on traditional CVD risk factors. Crude all-cause mortality rates were calculated per 1,000 person-years. Multivariable Cox proportional hazards regression assessed the association of traditional risk factors and CAC with mortality. Results: The mean age was 58.6 years old, 51.0% were women, 51.3% had prevalent CAC, and the median HDL-C was 100 mg/dL. There were 20 deaths (6.0%) over a median follow-up of 10.5 years, 7 (2.1%) of which were attributable to CVD. There was a stepwise higher crude mortality rate per 1,000 person-years across increasing CAC burden ( Central Illustration ). Independent of traditional risk factors, each 100 Agatston Unit increase in CAC score was associated with a 7% higher hazard of all-cause mortality (HR: 1.07, 95% CI: 1.01-1.12) and individuals with CAC &gt; 1000 experienced a 5.75-fold higher hazard of mortality when compared to CAC=0 (HR: 5.75, 95% CI: 1.26-26.24). Beyond age, no traditional risk factor was associated with mortality in multivariable analyses. Conclusion: Measurement of CAC on non-contrast cardiac computed tomography may facilitate risk assessment among individuals with very-high HDL-C.

Sex hormones and the risk of myocardial infarction in women and men: a prospective cohort study in the UK Biobank

ObjectivesThere is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank.MethodsThe UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40–69 years) women and men between 2006 and 2010.Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone–binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men.ResultsData were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women.ConclusionsA higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI.

Myocardial Infarction Within 30 Days of Discharge From an Emergency Department: A Descriptive Study of Albertan Women

BackgroundCardiovascular diseases (CVDs) are the leading cause of premature death for Canadian women, which may be due partly to a lack of awareness of the presentation of acute coronary events in emergency departments (EDs). To address an identified gap in women’s cardiovascular care, we sought to describe the clinical and comorbid factors of women who, following discharge from an ED, suffered a myocardial infarction (MI). MethodsDescriptive analyses were completed on a cohort of women who presented to an ED in Alberta, Canada, between January 1, 2010 and December 31, 2020, were discharged, and within 30 days of their index ED visit, were admitted to the hospital with an MI. The cohort was explored for clinical and comorbid data, ED visits pre-MI, type of MI, and presenting complaint/ primary diagnosis for the index ED visit. Results1380 women were included in this analysis with a mean age of 67 (standard deviation ±13) years. The frequencies of hypertension, diabetes, and dyslipidemia among the youngest women, aged 18-45 years, were 47.5%, 31.3%, and 48.8%, respectively. Women across all ages demonstrated a high prevalence of traditional CVD risk factors, and 22% of women presented to an ED 2 or more times within the 30 days pre-MI. ConclusionsRegardless of their age, the women in this cohort had notable CVD risk factors. Future research is required to better understand the phenomenon of women presenting multiple times to an ED pre-MI. Research is needed on life-stage–specific factors of women presenting to EDs pre-MI, to help reduce MI incidence.

Impact of puberty, sex determinants and chronic inflammation on cardiovascular risk in young people.

Worrying trends of increased cardiovascular disease (CVD) risk in children, adolescents and young people in the Modern Era have channelled research and public health strategies to tackle this growing epidemic. However, there are still controversies related to the dynamic of the impact of sex, age and puberty on this risk and on cardiovascular health outcomes later in life. In this comprehensive review of current literature, we examine the relationship between puberty, sex determinants and various traditional CVD-risk factors, as well as subclinical atherosclerosis in young people in general population. In addition, we evaluate the role of chronic inflammation, sex hormone therapy and health-risk behaviours on augmenting traditional CVD-risk factors and health outcomes, ultimately aiming to determine whether tailored management strategies for this age group are justified.

Low concentrations of medium-sized HDL particles predict incident CVD in chronic kidney disease patients

Patients with chronic kidney disease (CKD) are at high risk for CVD. However, traditional CVD risk factors cannot completely explain the increased risk. Altered HDL proteome is linked with incident CVD in CKD patients, but it is unclear whether other HDL metrics are associated with incident CVD in this population. In the current study, we analyzed samples from two independent prospective case-control cohorts of CKD patients, the Clinical Phenotyping and Resource Biobank Core (CPROBE) and the Chronic Renal Insufficiency Cohort (CRIC). We measured HDL particle sizes and concentrations (HDL-P) by calibrated ion mobility analysis and HDL cholesterol efflux capacity (CEC) by cAMP-stimulated J774 macrophages in 92 subjects from the CPROBE cohort (46 CVD and 46 controls) and in 91 subjects from the CRIC cohort (34 CVD and 57 controls). We tested associations of HDL metrics with incident CVD using logistic regression analysis. No significant associations were found for HDL-C or HDL-CEC in either cohort. Total HDL-P was only negatively associated with incident CVD in the CRIC cohort in unadjusted analysis. Among the six sized HDL subspecies, only medium-sized HDL-P was significantly and negatively associated with incident CVD in both cohorts after adjusting for clinical confounders and lipid risk factors with odds ratios (per 1-SD) of 0.45 (0.22–0.93, P = 0.032) and 0.42 (0.20–0.87, P = 0.019) for CPROBE and CRIC cohorts, respectively. Our observations indicate that medium-sized HDL-P—but not other-sized HDL-P or total HDL-P, HDL-C, or HDL-CEC—may be a prognostic cardiovascular risk marker in CKD.

PREVALENCE AND PATTERN OF DYSLIPIDEMIA AND ITS ASSOCIATED FACTORS IN CHRONIC KIDNEY DISEASE PATIENTS

A study of Lipid prole in CKD patient is subject of interest due to impact on the individual and society as dyslipidaemia is one of the traditional risk factors for CVD which is responsible for most of the morbidity &amp; mortality in CKD patient. And its study can lead to therapeutical result affecting both short term and long-term outcomes. To identify and analyse lipid AIMS &amp; OBJECTIVE - alteration in CKD patients and study the correlation between renal function and lipid abnormalities in CKD Our study is hospital METHODS – based descriptive observational study for duration of 18 months. Study included 100 patients RESULTS – in which mean age was 51.88 and male to female ratio of 1.5:1. Prevalence of Lipid Prole abnormalities seen as HDL decreased in 100% patient and Cholesterol, LDL, Triglyceride increased in 40%, 24%, 64% patients respectively Dyslipidaemia is common among pa CONCLUSION - tients with CKD and predominant lipid prole abnormalities were reduced HDL and elevated Triglycerides. Hence regular monitoring of lipid prole should be done in patients of CKD

Abstract TP80: Regional Trends And Variation In Mortality By Subgroups Following Mechanical Thrombectomy In Geriatric Acute Ischemic Stroke-related Hospitalizations In Urban Facilities, 2016-2019

Background: Mechanical thrombectomy (MT) has been proven to be a successful treatment option for patients with acute ischemic stroke (AIS) in numerous randomized controlled trials. The majority of trials underrepresent patients aged 70 and above, and there is little contemporary data on regional trends and variation in mortality. Methods: This retrospective study using the National Inpatient Sample (2016-2019) seeks to identify any regional relationships between geriatric patients' in-hospital mortality after MT for AIS at urban facilities and trends in inpatient mortality. Regional Inpatient mortality based on sex and race and trends between 2016 and 2019 were assessed. Results: Our study group consisted of 52455 AIS-MT admissions (median 78 yrs, 57.1% male, 77.2% white, 89.6% Medicare enrollees) with a 14.1% inpatient mortality rate. Despite having a lower comparative burden of traditional CVD risk factors, the hospitals from the Northeast had a higher inpatient mortality rate (17.2%, n=1650) and risk (adjusted OR:1.25, 95% CI:1.03-1.51) than the other regions. Similar trends were observed in male (18.1%), females (16.6%), white (17.3%) and black (13.8%) participants (P&lt;0.001) undergoing AIS-MT. Highest inpatient mortality among Hispanics was linked to Midwest-based participants (16.2%) without regional variation in rates for Asians. There were declining trends in mortality between 2016 to 2019 in West region without any change in other regions (from 14.0% to 11.5%, ptrend=0.002) (Fig. 1) . Conclusion: Among demographically comparable geriatric patients with AIS undergoing MT in the US, the Northeast region admissions showed the highest inpatient mortality even after controlling for confounding factors with a relatively lower burden of CVD risk factors. This disparity warrants further research to validate these findings.

The Role of Imaging in Preventive Cardiology in Women.

The prevalence of CVD in women is increasing and is due to the increased prevalence of CV risk factors. Traditional CV risk assessment tools for prevention have failed to accurately determine CVD risk in women. CAC has shown to more precisely determine CV risk and is a better predictor of CV outcomes. Coronary CTA provides an opportunity to determine the presence of CAD and initiate prevention in women presenting with angina. Identifying women with INOCA due to CMD with use of cPET or cMRI with MBFR is vital in managing these patients. This review article outlines the role of imaging in preventive cardiology for women and will include the latest evidence supporting the use of these imaging tests for this purpose. CV mortality is higher in women who have more extensive CAC burden. Women have a greater prevalence of INOCA which is associated with higher MACE. INOCA is due to CMD in most cases which is associated with traditional CVD risk factors. Over half of these women are untreated or undertreated. Recent study showed that stratified medical therapy, tailored to the specific INOCA endotype, is feasible and improves angina in women. Coronary CTA is useful in the setting of women presenting with acute chest pain to identify CAD and initiate preventive therapy. CAC confers greater relative risk for CV mortality in women versus (vs.) men. cMRI or cPET is useful to assess MBFR to diagnose CMD and is another useful imaging tool in women for CV prevention.

Exercise-induced specialized proresolving mediators stimulate AMPK phosphorylation to promote mitochondrial respiration in macrophages

ObjectivePhysical activity has been shown to reduce the risk of CVD mortality in large-cohort longitudinal studies; however, the mechanisms underpinning the beneficial effects of exercise remain incompletely understood. Emerging data suggest that the risk reducing effect of exercise extends beyond changes in traditional CVD risk factors alone and involves alterations in immunity and reductions in inflammatory mediator production. Our study aimed to determine whether exercise-enhanced production of proresolving lipid mediators contribute to alterations in macrophage intermediary metabolism, which may contribute to the anti-inflammatory effects of exercise. MethodsChanges in lipid mediators and macrophage metabolism were assessed in C57Bl/6 mice following 4 weeks of voluntary exercise training. To investigate whether exercise-stimulated upregulation of specialized proresolving lipid mediators (SPMs) was sufficient to enhance mitochondrial respiration, both macrophages from control mice and human donors were incubated in vitro with SPMs and mitochondrial respiratory parameters were measured using extracellular flux analysis. Compound-C, an ATP-competitive inhibitor of AMPK kinase activity, was used to investigate the role of AMPK activity in SPM-induced mitochondrial metabolism. To assess the in vivo contribution of 5-lipoxygenase in AMPK activation and exercise-induced mitochondrial metabolism in macrophages, Alox5−/− mice were also subjected to exercise training. ResultsFour weeks of exercise training enhanced proresolving lipid mediator production, while also stimulating the catabolism of inflammatory lipid mediators (e.g., leukotrienes and prostaglandins). This shift in lipid mediator balance following exercise was associated with increased macrophage mitochondrial metabolism. We also find that treating human and murine macrophages in vitro with proresolving lipid mediators enhances mitochondrial respiratory parameters. The proresolving lipid mediators RvD1, RvE1, and MaR1, but not RvD2, stimulated mitochondrial respiration through an AMPK-dependent signaling mechanism. Additionally, in a subset of macrophages, exercise-induced mitochondrial activity in vivo was dependent upon 5-lipoxygenase activity. ConclusionCollectively, these results suggest that exercise stimulates proresolving lipid mediator biosynthesis and mitochondrial metabolism in macrophages via AMPK, which might contribute to the anti-inflammatory and CVD risk reducing effect of exercise.

Abstract 13648: Risk Profile and Prognostic Implications of Premature Advanced Atherosclerotic Disease Among Young Adults: The Coronary Artery Calcium Consortium

Introduction: Advanced atherosclerotic disease among young adults is an under-recognized and unique disease phenotype that has not been well characterized. Methods: We used data from 23,706 participants aged 30-50 years (mean age 43.9 ± 4.6 years; 74.7% men) from the Coronary Artery Calcium (CAC) Consortium, a cohort of individuals with no prior CVD history referred for CAC scanning. We defined advanced disease as CAC ≥ 90 th percentile for age, sex, and race, and compared risk factor profile of persons with advanced disease to those without CAC and those with CAC &lt; 90 th percentile. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we assessed the association of advanced disease with all-cause, cardiovascular (CV), and CHD mortality. Results: Of the 23,706 participants, 8,289 (35%) had CAC. Among them, 3,549 (43%) had CAC ≥ 90 th percentile. Compared to persons without CAC and those with CAC &lt; 90 th percentile, those with CAC ≥ 90 th had higher prevalence of all the traditional CVD risk factors. Notably, 56% of those with CAC ≥ 90 th percentile had ≥ 2 risk factors, and 68% already had multivessel CAC compared to 34% of those with CAC &lt; 90 th percentile. After a mean follow-up of 12.6 ± 3.6 years, the incidence of all-cause, CV, and CHD mortality was highest in those with advanced disease. Persons with CAC ≥ 90 th percentile had a higher multivariable-adjusted risk of all-cause (HR 2.11 [1.62 - 2.73]), CV (SHR 2.88 [1.74 - 4.78]), and CHD mortality (SHR 4.41 [2.16 - 8.98]), compared to those without CAC. When compared to those with CAC &lt; 90 th percentile, only those with CAC ≥ 90 th percentile had significantly higher risk of all-cause, CV, and CHD mortality ( Figure ). Conclusions: Premature advanced atherosclerosis is a distinct clinical phenotype that strongly predicts all-cause and cause-specific mortality. Among persons with CAC at young age, those with scores ≥ 90th percentile have the highest risk of early death and should be a focus of clinical prevention.

Abstract 13139: Explainable Machine Learning Model for Prediction of Cardiovascular Disease With Routinely Collected Clinical Data Combined With Publicly Available Data on Environmental Risk Factors

Introduction: Little is known about the performance benefit of combining these data with publicly available environmental risk factors for CVD prediction models. Hypothesis: We aimed to test whether routinely collected clinical data (age, sex, systolic blood pressure, total cholesterol, cigarette smoking) in combination with data on environmental risk factors could improve the performance of CVD prediction using an explainable machine learning (ML) technique. Methods: We identified individuals without previous history of CVD from the National Health Insurance Service, 2002-2015 in the Republic of Korea, linked to publicly available data on annual average of fine particulate matter (PM 10 ) exposure and urban green space coverage according to the administrative code for residence in each individual. Random forest (RF) model and SHapley Additive exPlanations (SHAP) value were used for prediction for newly diagnosed CVD and explanation for contribution of each component to the model output, respectively. Performance of the prediction models were evaluated using area under the curve (AUC). Results: Among 151,936 individuals included, there were 2,837 subsequent CVD events. The AUCs for the RF model with the clinical data only and the model with environmental risk factors (high annual average PM 10 and low UGS coverage) in addition to the clinical data were 0.731 and 0.733, respectively. The SHAP values showed that adding these environmental risk factors did not have significant impact on the model output (SHAP summary plot). However, the clinical data comprised of traditional CVD risk factors had notable contribution to the performance of prediction model. Conclusions: This study showed that adding publicly available data on environmental risk factors to the routinely collected clinical data had only marginal improvement in the prediction of CVD outcomes.