Burden Of Atherosclerotic Cardiovascular Disease Research Articles

LDL-C target attainment and statin use in patients with ASCVD, familial hypercholesterolaemia, and those otherwise at moderate/high-risk of ASCVD in australian general practice (SCOPE-GP)

Abstract Background The proportion of Australian general practice patients not attaining low-density lipoprotein cholesterol (LDL-C) goals is not well described. The SCOPE-GP study evaluated duration of LDL-C exceeding treatment goals, statin use and discontinuation rates in patients with atherosclerotic cardiovascular disease (ASCVD), without ASCVD events but at moderate/high-risk, and familial hypercholesterolemia (FH). Methods This population-based retrospective cohort study used de-identified medical records of adult patients captured in the IQVIA GP-EMR database. Patients were indexed at the earliest date of ASCVD, FH, or hyperlipidemia diagnosis from January 1, 2010 to June 30, 2022, with a variable follow-up period from index to June 30, 2022. Ascertainment of study cohort was based on the 2021 ESC/EAS guidelines and Framingham Risk Equation. LDL-C test result levels were extracted per patient, summarised and analysed. Patients were stratified based on their test results at latest results/closest to censor date. Average time above target levels is the proportion of number of days above LDL-C target levels over total number of follow-up days for each patient. A Poisson distribution was fitted to estimate 95% confidence interval. Lipid lowering therapies (LLT) were stratified by (ASCVD, FH and moderate/high risk of CVD) at last visit/censor date. Combination of LLT were defined as prescriptions for fixed dose combinations or ≥2 separate scripts of LLT from different classes within 180 days from last visit/censor date (look back period). Discontinuation is defined as no statins were prescribed again after the last script for 270 days or more, limited to the first occurrence. Results The average time with LDL-C levels above target was 1077.5 days in ASCVD patients (n=2,688), 938.6 days in moderate-risk ASCVD (n=37,003), 980.9 days in high-risk ASCVD (n=85,199), and 900.8 days in FH (n=279). The proportion of days above target level for all four cohorts is described in Figure 1. Among 107,552 patients with recorded LDL-C levels ≥1.8mmol/L at their last visit/censor date, 30.9% were on statin monotherapy and 1.0% were on statin+ezetimibe. Statin use was highest in ASCVD patients (65.4%), followed by FH (49.5%), high risk (40.0%) and moderate risk subjects (29.5%) (Table 1). Statin discontinuation rates were 60.3%, 76.3, 66.1%, and 65.8% in these groups, respectively. The predominant reason for statin discontinuation was non-specific adverse drug reactions (12.2% ASCVD, 11.7% moderate-risk, 13.2% high-risk and 17.9% FH). The proportion of subjects contraindicated to statins was highest in moderate risk subjects (0.05%). Conclusions Prolonged periods of elevated LDL-C and high statin discontinuation rates were prevalent among at-risk individuals in Australian primary care. This underscores a significant ASCVD burden that could be prevented with more active lipid management.

Hypercholesterolemia and inflammation-Cooperative cardiovascular risk factors.

Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events.In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation. Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering. Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.

Trends in type 2 diabetes medication use and guideline adherence in Belgian primary care (2019–2023)

AimsTo assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD) among patients with type 2 diabetes (T2D) in Belgium. To analyze trends in medication use and adherence to guidelines from 2019 to 2023. MethodsWe conducted a retrospective cross-sectional analysis using data from the Intego primary care database, encompassing records from 431 general practitioners. We identified adults with T2D through diagnostic codes and glycated hemoglobin levels and analyzed subgroups with ASCVD, HF, and CKD for trends in medication use, particularly SGLT2 inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP-1). ResultsThe T2D population increased from 20,766 in 2019 to 21,764 in 2023. The prevalence of ASCVD, HF, and CKD among T2D patients slightly increased to 27 %, 6.7 %, and 23.7 % by 2023 (from 25.2 %, 4.9 % and 21.5 % respectively). Medication prescription trends showed a tripling of SGLT2-i and GLP-1 prescribing in the study period to 6.2 % and 11.5 % respectively. Despite these increases, only 7.5 % of eligible patients received these medications as of 2023. ConclusionThe study highlights a growing burden of ASCVD, HF, and CKD among T2D patients in Belgium and an increase in the use of guideline-recommended medications. However, there remains a substantial gap in the optimal use of these therapies, indicating a need for improved implementation of clinical guidelines in primary care.

A mixed-methods, theory-driven assessment of the sustainability of a multi-sectoral preventive intervention for South Asian Americans at risk for cardiovascular disease

BackgroundSouth Asian Americans bear a high burden of atherosclerotic cardiovascular disease (ASCVD), but little is known about the sustainability of evidence-based interventions (EBI) to prevent ASCVD in this population. Using community-based participatory research, we previously developed and implemented the South Asian Healthy Lifestyle Intervention (SAHELI), a culturally-adapted EBI targeting diet, physical activity, and stress management. In this study, we use the Integrated Sustainability Framework to investigate multisectoral partners’ perceptions of organizational factors influencing SAHELI sustainability and strategies for ensuring sustainability.MethodsFrom 2022 to 2023, we conducted a mixed-methods study (quant- > QUAL) with 17 SAHELI partners in the Chicago area. Partners’ settings included: community organization, school district, public health department, and healthcare system. Descriptive statistics summarized quantitative results. Two coders used a hybrid thematic analysis approach to identify qualitative themes. Qualitative and quantitative data were integrated and analyzed using mixed methods.ResultsSurveys (score range 1–5: higher scores indicate facilitators; lower scores indicate barriers) indicated SAHELI sustainability facilitators to be its “responsiveness to community values and needs” (mean = 4.9). Barriers were “financial support” (mean = 3.5), “infrastructure/capacity to support sustainment” (mean = 4.2), and “implementation leadership” (mean = 4.3). Qualitative findings confirmed quantitative findings that SAHELI provided culturally-tailored cardiovascular health education responsive to the needs of the South Asian American community, increased attention to health issues, and transformed perceptions of research among community members. Qualitative findings expanded upon quantitative findings, showing that the organizational fit of SAHELI was a facilitator to sustainability while competing priorities were barriers for partners from the public health department and health system. Partners from the public health department and health system discussed challenges in offering culturally-tailored programming exclusively for one targeted population. Sustainability strategies envisioned by partners included: transitioning SAHELI to a program delivered by community members; integrating components of SAHELI into other programs; and expanding SAHELI to other populations. Modifications made to SAHELI (i.e., virtual instead of in-person delivery) had both positive and negative implications for sustainability.DiscussionThis study identifies common sustainability barriers and facilitators across different sectors, as well as those specific to certain settings. Aligning health equity interventions with community needs and values, organizational activities, and local context and resources is critical for sustainability. Challenges also arise from balancing the needs of specific populations against providing programming for broader audiences.

The Economic Burden of Atherosclerotic Cardiovascular Disease in Italy.

Atherosclerotic cardiovascular diseases remain the primary cause of mortality in Italy. Individuals with a history of acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack face an elevated risk of recurrent major adverse cardiovascular events, including mortality. The population aging, coupled with increasing risk factors such as diabetes mellitus and obesity, exacerbates the disease's economic impact. This study aims to comprehensively assess the economic burden of atherosclerotic cardiovascular diseases in Italy, specifically focusing on direct healthcare costs. We analyzed real-world data from administrative databases in the Marche region and Local Health Unit Umbria 2. The economic burden of patients discharged with acute coronary syndrome, peripheral arterial disease, and ischemic stroke/transient ischemic attack was evaluated, with a focus on direct costs associated with hospitalizations, drugs, and outpatient visits. Results were stratified by age, sex, comorbidities at baseline, and adherence to lipid-lowering therapy and antihypertensive agents. Annually, nearly 350,000 patients were hospitalized for peripheral arterial disease, acute coronary syndrome, or ischemic stroke/transient ischemic attack. Direct health costs averaged €7190 per patient over a 2-year follow-up, with hospitalizations accounting for nearly 70% of the total. Male patients incurred significantly higher costs (€7467) than female patients (€6625). Costs correlated positively with age and with the number of baseline comorbidities, with a range from €5259 (0-1 comorbidities) to €17,095 (4+ comorbidities). Costs were significantly lower in adherent subjects (€6813) compared with non-adherent subjects (€7757). This study provides valuable insights into the economic implications of atherosclerotic cardiovascular diseases in Italy, emphasizing the necessity of a comprehensive approach to preventive measures, optimal medication adherence, and lifestyle modifications to mitigate its impact.

Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study

Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. For the Spanish translation of the abstract see Supplementary Materials section.

Comparative analysis of atherosclerotic cardiovascular disease burden between ages 20–54 and over 55 years: insights from the Global Burden of Disease Study 2019

BackgroundTo systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults.MethodsWe estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20–54 and > 55 years from 1990–2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications.ResultsFrom 1990–2019, the global prevalence rates of IHD, IS, and PAD in the 20–54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20–54 years group than in the > 55 years group. For PAD, DALYs among those aged 20–54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals.ConclusionsThe ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

The Hurdle of Access to Emerging Therapies and Potential Solutions in the Management of Dyslipidemias.

This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for the prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, and regulatory barriers significantly impede access to LLTs, exacerbating disparities in healthcare infrastructure and affordability. We highlight the importance of policy reforms, including pricing regulations and reimbursement policies, for enhancing affordability and streamlining regulatory processes. Innovative funding models, such as value-based pricing and outcome-based payment arrangements, have been recommended to make novel LLTs more accessible. Public health interventions, including community-based programs and telemedicine, can be utilized to reach underserved populations and improve medication adherence. Education and advocacy initiatives led by patient advocacy groups and healthcare providers play a crucial role in raising awareness and empowering patients. Despite the barriers to access, novel LLTs present a big opportunity to reduce the burden of ASCVD, emphasizing the need for collaborative efforts among policymakers, healthcare providers, industry stakeholders, and patient advocacy groups to address these barriers to improve access to LLTs globally.

Epidemiology and current management of cardiovascular disease in China.

The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. This is the fourth section of the report with a specific focus on epidemiology and current management of cardiovascular disease (CVD) in China. This section of the report highlights the epidemiological trends of CVD in China. It reveal a concerning rise in prevalence, with approximately 330 million affected individuals, including significant numbers with stroke, coronary artery disease (CAD), heart failure, and other conditions. CVD stands as the primary cause of mortality among both urban and rural populations, accounting for nearly half of all deaths in 2020. Mortality rates are notably higher in rural areas compared to urban centers since 2009. While age-standardized mortality rates have decreased, the absolute number of CVD deaths has increased, primarily due to population aging. Ischemic heart disease, hemorrhagic and ischemic strokes are the leading causes of CVD-related deaths. Notably, the burden of atherosclerotic cardiovascular disease has risen substantially, with atherosclerotic cardiovascular disease-related deaths increasing from 1990 to 2016. The incidence of ischemic stroke and ischemic heart disease has shown similar increasing trends over the past three decades. CAD mortality, particularly acute myocardial infarction, has been on the rise, with higher mortality rates observed in rural areas since 2016. The prevalence of CAD has increased significantly, with over 11 million patients identified in 2013. Studies assessing hospital performance in managing acute coronary syndrome reveal gaps in adherence to guideline-recommended strategies, with disparities in care quality across hospitals. However, initiatives like the China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Retrospective AMI Study and the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project aim to improve patient outcomes through enhanced care protocols. Moreover, advancements in medical technology, such as quantitative flow ratio-guided lesion selection during percutaneous coronary intervention, show promise in improving clinical outcomes for patients undergoing intervention.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Closing the Gaps in Care of Dyslipidemia: Revolutionizing Management with Digital Health and Innovative Care Models.

Although great progress has been made in the diagnostic and treatment options for dyslipidemias, unawareness, underdiagnosis and undertreatment of these disorders remain a significant global health concern. Growth in digital applications and newer models of care provide novel tools to improve the management of chronic conditions such as dyslipidemia. In this review, we discuss the evolving landscape of lipid management in the 21st century, current treatment gaps and possible solutions through digital health and new models of care. Our discussion begins with the history and development of value-based care and the national establishment of quality metrics for various chronic conditions. These concepts on the level of healthcare policy not only inform reimbursements but also define the standard of care. Next, we consider the advances in atherosclerotic cardiovascular disease risk score calculators as well as evolving imaging modalities. The impact and growth of digital health, ranging from telehealth visits to online platforms and mobile applications, will also be explored. We then evaluate the ways in which machine learning and artificial intelligence-driven algorithms are being utilized to address gaps in lipid management. From an organizational perspective, we trace the redesign of medical practices to incorporate a multidisciplinary team model of care, recognizing that atherosclerotic cardiovascular disease risk is multifaceted and requires a comprehensive approach. Finally, we anticipate the future of dyslipidemia management, assessing the many ways in which atherosclerotic cardiovascular disease burden can be reduced on a population-wide scale.

Eradicating Atherosclerotic Events by Targeting Early Subclinical Disease: It Is Time to Retire the Therapeutic Paradigm of Too Much, Too Late.

Recent decades have seen spectacular advances in understanding and managing atherosclerotic cardiovascular disease, but paradoxically, clinical progress has stalled. Residual risk of atherosclerotic cardiovascular disease events is particularly vexing, given recognized lifestyle interventions and powerful modern medications. Why? Atherosclerosis begins early in life, yet clinical trials and mechanistic studies often emphasize terminal, end-stage plaques, meaning on the verge of causing heart attacks and strokes. Thus, current clinical evidence drives us to emphasize aggressive treatments that are delayed until patients already have advanced arterial disease. I call this paradigm "too much, too late." This brief review covers exciting efforts that focus on preventing, or finding and treating, arterial disease before its end-stage. Also included are specific proposals to establish a new evidence base that could justify intensive short-term interventions (induction-phase therapy) to treat subclinical plaques that are early enough perhaps to heal. If we can establish that such plaques are actionable, then broad screening to find them in early midlife individuals would become imperative-and achievable. You have a lump in your coronaries! can motivate patients and clinicians. We must stop thinking of a heart attack as a disease. The real disease is atherosclerosis. In my opinion, an atherosclerotic heart attack is a medical failure. It is a manifestation of longstanding arterial disease that we had allowed to progress to its end-stage, despite knowing that atherosclerosis begins early in life and despite the availability of remarkably safe and highly effective therapies. The field needs a transformational advance to shift the paradigm out of end-stage management and into early interventions that hold the possibility of eradicating the clinical burden of atherosclerotic cardiovascular disease, currently the biggest killer in the world. We urgently need a new evidence base to redirect our main focus from terminal, end-stage atherosclerosis to earlier, and likely reversible, human arterial disease.

Epigenetically-driven persistence of inflammatory and oxidative phenotypes in adolescents born to women with gestational diabetes

Abstract Background According to the theory of developmental origins of health and disease1, environmental changes during the in-utero period can permanently affect health and vulnerability to diseases later in life. As a matter of fact, the offspring of women with gestational diabetes (GD) exhibit a higher risk for developing obesity, type 2 diabetes (T2D), and atherosclerotic cardiovascular disease (ASCVD) than those individuals with a family history of diabetes2–4. Importantly, epigenetics has emerged as a crucial determinant for this transmission across generations5–8. Mixed Lineage Leukemia 1 (MLL1) histone methyltransferase activates inflammatory and oxidative pathways through trimethylation of histone 3 at lysine 4 amino (H3K4me3)9. Purpose To investigate whether such epigenetic mark regulates genes triggering inflammation and oxidative stress in GD women, and its potential transmission and persistence in their offspring. Methods We isolated peripheral blood mononuclear cells (PBMCs), fetal cord blood mononuclear cells (CBMCs), and umbilical cord vein endothelial cells (HUVECs) from GD and control pregnant women, as well as PBMCs and plasma samples from a retrospective cohort of adolescents (12-16 years old) born to control or GD women. Gene and protein expressions were investigated by RT-PCR, immunoblotting and/or confocal microscopy. H3K4me3 levels on NF-kB p65 and NADPH oxidase isoform 4 (NOX4) promoter regions were assessed by chromatin immunoprecipitation (ChIP) and RT-PCR. Mechanistic studies were performed in control- and GD-HUVECs using the MLL1 inhibitor MM-102 to assess downstream inflammatory mediators and superoxide anion (O2-) generation by electron spin resonance (ESR) spectroscopy. Results Our data showed upregulation of MLL1 and H3K4me3 levels in PBMCs, HUVECs, and CBMCs isolated from GD as compared to control women. ChIP analysis revealed H3K4me3 enrichment in the promoter region of the inflammatory and oxidative master regulatory genes NF-kB p65 and NOX4, respectively, in these cells. We also found an upregulation of NF-kB p65 target genes IL-6, MCP-1, ICAM-1, and VCAM-1, and increased monocyte adhesion and O2- production. The inhibition of MLL1 was able to reduce H3K4me3 levels blunting the inflammatory and oxidative phenotypes in GD-HUVECs. Interestingly enough, we demonstrated a persistent increase of H3K4me3 in the NF-kB p65 promoter region of PBMCs together with an elevation of inflammatory markers in plasma from adolescents born to GD women. Conclusions Our results suggest that GD may induce inflammation and oxidative stress through MLL1-dependent H3K4me3 mechanisms. Such epigenetic mark is transmitted to the offspring and, most importantly, can still be found in adolescence as a pro-inflammatory trigger. These findings pave the way for pharmacological reprogramming of adverse histone modifications to counteract early abnormal phenotypes in GD offspring which may accelerate ASCVD burden.

Abstract 13692: Incidence, Recurrence, and Ethnicity Specific Risk Factors for Premature Coronary Artery Disease in South Asians and Europeans

Introduction: Premature coronary artery disease (CAD) incidence is increasing globally. South Asians (SA) have a disproportionately high burden of atherosclerotic cardiovascular disease (ASCVD). However, the effect of SA ethnicity on the risk of recurrent events in patients with premature CAD has not been prospectively evaluated. Methods: Patients in the SAVEBC and UK biobank (UKB) registries were enrolled and stratified by ethnicity and presence of premature CAD. The co-primary outcomes were to compare proportion of premature CAD and the incidence of recurrent ASVCD events. Secondary exploratory outcomes included describing demographic, physical, biochemical variables between cohorts. Results: 11,136 patients were included, 1,129 (143 SA; 21%) were from SAVEBC and 10,007 (400 SA; 4.0%) from UKB. There was a higher proportion of premature CAD in SA compared to Caucasians in UKB (5.2% vs. 2.0%, p &lt; 0.001). Similarly, SA were overrepresented in SAVEBC (21% of cohort vs. 7.9% of British Columbia population). SA compared to Caucasians with premature CAD had increased prevalence of diabetes (SAVEBC: 20.1% vs 13.8%, p=0.08; UKB: 37.5% vs 18.0%, p&lt;0.001), and lower mean HDL cholesterol (SAVEBC: 1.4±0.4 vs 1.5±0.4, p=0.21; UKB: 1.1±0.3 vs 1.2±0.3, p&lt;0.001). SA had more diffuse disease reflected by more coronary segments affected (4.9±3.0 vs. 4.1±2.6, p=0.05), and a trend towards more affected coronary vessels compared to Caucasians (1.31±1.4 vs. 0.61±0.91, p=0.14). SA had greater incidence of recurrent ASCVD vs. Caucasians (4.19 vs. 3.08 events per 100 P-Y; incidence rate ratio p-value &lt; 0.001). SA had higher risk of recurrent ASCVD events (HR 1.35, 95% CI 1.13,1.61, p&lt;0.001). SA ethnicity remained a predictor of recurrent events on adjusted COX regression (HR 1.24, 95% CI 1.03,1.48, p=0.02). Conclusion: Using two prospective registries, SA had a higher proportion of premature CAD and recurrent cardiovascular events with shorter time to recurrent events. Some risk may be explained by adverse cardiometabolic profiles, however significant risk mechanisms are yet to be elucidated. Understanding the unique mechanisms of cardiovascular risk in SA is critical to appropriately identify high-risk individuals and initiate contemporary preventative therapies.

Abstract 15536: Impact of Social Determinants of Health on Atherosclerotic Cardiovascular Diseases Incidence

INTRODUCTION: Individuals with an unfavorable socioeconomic status have a higher risk of developing chronic diseases such as atherosclerotic cardiovascular disease (ASCVD). However, the shared contribution of socioeconomic status, psychosocial factors and living environment on ASCVD risk remains unknown. We investigated the contribution of these social determinants of health on the incidence of ASCVD. METHODS: We developed a polysocial risk score (PsRS) using latent class analysis based on socioeconomic factors (household income, level/quality of education and employment status), psychosocial factors (living alone, social support, social activities, social isolation, emotional distress, and diagnosis of psychiatric disorders), and living environment (social deprivation score, crime rate, housing quality, housing stability, proximity to green/blue spaces and proximity to nature). The study sample included 319 842 participants of the UK Biobank, free of ASCVD recruited between 2006 and 2010. As of August 2021, 23 840 of them had incident ASCVD (fatal or nonfatal myocardial infarction, ischemic stroke, or cardiac revascularization procedures). Participants were divided into three groups based on latent class analysis adjusted for age. The impact of the PsRS on incident ASCVD was assessed using Cox proportional hazards for all participants, women and men adjusted for age, sex, and ethnicity. RESULTS: Compared to participants with a low PsRS, those with an intermediate score had a slightly higher risk of ASCVD (hazard ratio [HR]=1.05 [95% CI, 1.01-1.09], p=0.024) while those with a high PsRS had a higher risk of ASCVD (HR=1.46 [95% CI, 1.40-1.52], p&lt;0.001). The effect of the PsRS on ASCVD incidence appeared to be more pronounced in women (HR=1,59 [95% CI, 1.48-1.71], p&lt;0.001 and HR=1.39 [95% IC, 1.32-1.46], p&lt;0.001, respectively, for women and men with a high PsRS compared to individuals with a low PsRS within the same sex). CONCLUSION: A PsRS based on the living environment as well as socioeconomic and psychosocial factors was associated with incident ASCVD in participants of the UK Biobank. Multifactor approaches targeting both social determinants of health and traditional risk factors could reduce the burden of ASCVD in the general population.

Economic burden of atherosclerotic cardiovascular disease: a matched case–control study in more than 450,000 Swedish individuals

AimTo examine direct and indirect costs, early retirement, cardiovascular events and mortality over 5 years in people with atherosclerotic cardiovascular disease (ASCVD) and matched controls in Sweden.MethodsIndividuals aged ≥ 16 years living in Sweden on 01 January 2012 were identified in an existing database. Individuals with ASCVD were propensity score matched to controls without ASCVD by age, sex and educational status. We compared direct healthcare costs (inpatient, outpatient and drug costs), indirect costs (resulting from work absence) and the risk of stroke, myocardial infarction (MI) and early retirement.ResultsAfter matching, there were 231,417 individuals in each cohort. Total mean per-person annual costs were over 2.5 times higher in the ASCVD group versus the controls (€6923 vs €2699). Indirect costs contributed to 60% and 67% of annual costs in the ASCVD and control groups, respectively. Inpatient costs accounted for ≥ 70% of direct healthcare costs. Cumulative total costs over the 5-year period were €32,011 in the ASCVD group and €12,931 in the controls. People with ASCVD were 3 times more likely to enter early retirement than controls (hazard ratio [HR] 3.02 [95% CI 2.76–3.31]) and approximately 2 times more likely to experience stroke (HR 1.83 [1.77–1.89]) or MI (HR 2.27 [2.20–2.34]).ConclusionASCVD is associated with both economic and clinical impacts. People with ASCVD incurred considerably higher costs than matched controls, with indirect costs resulting from work absence and inpatient admissions being major cost drivers, and were also more likely to experience additional ASCVD events.

2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Atherosclerotic Cardiovascular Disease (ASCVD) risk assesment among healthy Indonesian Navy Personnel in East Java, Indonesia

Indonesia, as the largest archipelagic country, has a military population of its own. Atherosclerotic Cardiovascular Disease (ASCVD) are common in in Indonesian Navy personnel populations, and recent studies reported an increasing ofits prevalence.However, the data on specific navy military populations are still limited. This study aims to assess ASCVD risk on Indonesian navy personnel. This study use yearly medical check-up data of the Indonesian navy with high rank (fleet commander) aged 25-60 years old in period of January-August 2023. Those who already diagnosed with coronary artery disease were excluded. We use Framingham risk score and EUROS II Score to assess the ASCVD risk among samples. A total of 503 samples were recruited, 474 were male. Mean of age was 45 y.o, predominantly they were active smoker (64,8%) and overweight (44,5%). Among men’s population, the Framingham risk score shows almost half of the samples are at medium risk of ASCVD (40,16%), while a small percentage (17,3%) are at high risk as well as EuroSCORE II show remarkbly 62,21% of high ASCVD risk. The medium to high ASCVD risk among Indonesian Navy personnel need further attention and evaluation. A failure to give a decent preventive intervention may increase the burden of ASCVD in the future.