Burden Of Atherosclerotic Cardiovascular Disease Research Articles

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.

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.

Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society.

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women.

In-Hospital Mortality Outcomes of ST-Segment Elevation Myocardial Infarction: A Cross-Sectional Study from a Tertiary Academic Hospital in Johannesburg, South Africa.

In sub-Saharan Africa, the burden of atherosclerotic cardiovascular disease (ASCVD) is increasing. This study aimed to describe the clinical characteristics of patients with ST-segment elevation myocardial infarction (STEMI) and estimate the in-hospital all-cause mortality rate. We conducted a cross-sectional retrospective single-centre study of STEMI patients who underwent diagnostic coronary angiography with or without percutaneous coronary intervention (PCI) between January 2015 and December 2019. We compared demographic and clinical parameters between survivors and non-survivors with descriptive statistics. Univariable and multivariable logistic regression analyses were performed to determine the predictors of all-cause mortality. The study population consisted of 677 patients with a mean age of 55.5 ± 11.3 years. The in-hospital all-cause mortality rate was 6.2% [95% confidence interval (CI): 4.5-8.3%]. Risk factors for ASCVD included smoking (56.1%), hypertension (52.8%), dyslipidemia (40.0%), and a family history of coronary artery disease (32.7%). A pharmaco-invasive management strategy (treatment with thrombolytic therapy and PCI) was implemented in 36.5% of patients and reduced all-cause mortality risk (OR: 0.16; CI: 0.04-0.71, p = 0.015). The in-hospital all-cause mortality rate in STEMI patients was 6.2%, and a pharmaco-invasive management strategy proved to be an effective approach.

A novel therapeutic vaccine targeting the soluble TNFα receptor II to limit the progression of cardiovascular disease: AtheroVax™.

The burden of atherosclerotic cardiovascular disease contributes to a large proportion of morbidity and mortality, globally. Vaccination against atherosclerosis has been proposed for over 20 years targeting different mediators of atherothrombosis; however, these have not been adequately evaluated in human clinical trials to assess safety and efficacy. Inflammation is a driver of atherosclerosis, but inflammatory mediators are essential components of the immune response. Only pathogenic forms of sTNFR2 are acted upon while preserving the membrane-bound (wild-type) TNFR2 contributions to a non-pathogenic immune response. We hypothesize that the inhibition of sTNRF2 will be more specific and offer long-term treatment options. Here we describe pre-clinical findings of an sTNFR2-targeting peptide vaccine (AtheroVax™) in a mouse model. The multiple pathways to synthesis of the soluble TNFRII receptor (sTNFRII) were identified as sTNFRII(PC), sTNFRII(Δ7), and sTNFRII(Δ7,9). The sTNFRII(Δ7) peptide, NH2-DFALPVEKPLCLQR-COOH is specific to sTNFR2 based on an mRNA splice-variant in which exon 6 is joined to exon 8. The role of sTNFRII(Δ7) as a mediator of prolonged TNFα activity by preventing degradation and clearance was investigated. Inflammation is a critical driver of onset, progression and expansion of atherosclerosis. The TNFα ligand represents a driver of inflammation that is mediated by a splice variant of TNFR2, referred to as sTNFRII(Δ7). The multiple forms of TNFRII, both membrane bound and soluble, are associated with distinctly different phenotypes. sTNFRII(PC) and sTNFRII(Δ7) are not equivalent to etanercept because they lack a clearance mechanism. The unique peptide associated with sTNFRII(Δ7) contains a linear B-cell epitope with amino acids from both exon 6 and exon 8 supporting the vaccine design. Animal studies to evaluate the vaccine are ongoing, and results will be forthcoming. We describe a peptide vaccine targeting sTNFR2 in limiting the progression of atherosclerosis. A therapeutic vaccine limiting the progression of atherosclerosis will greatly contribute to the reduction in morbidity and mortality from cardiovascular disease. It is likely the vaccine will be used in combination with the current standards of care and lifestyle modifications.

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

Lipoprotein Apheresis: Current Recommendations for Treating Familial Hypercholesterolemia and Elevated Lipoprotein(a).

Familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) are relatively common disorders, posing a significant health burden due to increased risk of atherosclerotic cardiovascular disease (ASCVD). Development of electronic health record-based strategies with a linkage to the genetic test results has increased awareness, detection, and control of heritable lipid disorders. This review attempts to critically examine available data to provide a summary of the current evidence for lipoprotein apheresis in FH and elevated lipoprotein(a) (Lp(a)). Availability and indications for lipoprotein apheresis vary across the globe. On average, greater than 60% of atherogenic apoB-containing lipoproteins are immediately reduced following a single procedure, translating in substantial reduction of incident ASCVD events, and preventing accelerated vascular aging. Simultaneous lipid-lowering therapy targeting low-density lipoprotein (LDL) and Lp(a) enhances the efficacy of lipoprotein apheresis. Lipoprotein apheresis alters the proteomics of the lipoprotein particles, including reduction in the concentration of the oxidized-LDL and Lp(a) particles, and proinflammatory apoE bound to HDL particles and remnant lipoproteins. Other effects attributed to lipoprotein apheresis include improvement in blood rheology, endothelial function, microvascular flow, myocardial perfusion, reduction in circulating inflammatory markers. Development of lipoprotein apheresis registries provides data on benefits, challenges, and barriers to inform pertinent healthcare policies. Lipoprotein apheresis is a safe and effective procedure for lowering cholesterol in patients with combined and isolated FH and elevated Lp(a). It reduces the burden of ASCVD and improves long-term prognosis. A team approach is required by the patient, medical staff, and healthcare provider to initiate and maintain a lipoprotein apheresis program.

Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database

Background and aimsFamilial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets. MethodsWe performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH. ResultsProbable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18–29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels. ConclusionsThis nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients.

Estimating the Prevalence of Hypercholesterolemia in Indigenous Populations: A Systematic Review and Meta-Analysis

BackgroundHypercholesterolemia is a common condition characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of atherosclerotic cardiovascular disease (ASCVD). Indigenous populations experience disproportionate rates of ASCVD, however, the extent to which hypercholesterolemia contributes to this burden is unknown. ObjectivesThis study aimed to estimate the prevalence of hypercholesterolemia, severe hypercholesterolemia, and familial hypercholesterolemia (FH) in Indigenous populations in Canada, the United States, Australia, and New Zealand. MethodsWe searched MEDLINE, EMBASE, Web of Science, Native Health Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for peer-reviewed studies reporting on hypercholesterolemia and elevated LDL-C in Indigenous populations. All diagnostic criteria used to classify hypercholesterolemia were included. Pooled prevalence and 95% CIs were calculated using a random-effects model. ResultsThere were no studies reporting the prevalence of FH and one study reporting the prevalence of severe hypercholesterolemia in Indigenous populations. The pooled prevalence of hypercholesterolemia was 28.9% or ∼1 in 3 to 1 in 4 individuals (95% CI: 22.4%-36.4%) and 12.6% (95% CI: 7.7%-19.9%) using an LDL-C cutoff of ≥3.5 mmol/L (135 mg/dL). The pooled prevalence in Indigenous populations in North America was 24.3% (95% CI: 17.1%-33.3%) compared with 40.0% (95% CI: 31.3%-49.3%) in Australia. Meta-regression showed diabetes had a significant effect on prevalence (P = 0.022). ConclusionsHypercholesterolemia is prevalent in Indigenous communities and may contribute to the high burden of ASCVD these populations face. There is insufficient research on FH and severe hypercholesterolemia in Indigenous populations worldwide.

Prevalence of Statin Use for Primary Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and 10-Year Disease Risk in the US

The burden of atherosclerotic cardiovascular disease (ASCVD) in the US is higher among Black and Hispanic vs White adults. Inclusion of race in guidance for statin indication may lead to decreased disparities in statin use. To evaluate prevalence of primary prevention statin use by race and ethnicity according to 10-year ASCVD risk. This serial, cross-sectional analysis performed in May 2022 used data from the National Health and Nutrition Examination Survey, a nationally representative sample of health status in the US, from 2013 to March 2020 (limited cycle due to the COVID-19 pandemic), to evaluate statin use for primary prevention of ASCVD and to estimate 10-year ASCVD risk. Participants aged 40 to 75 years without ASCVD, diabetes, low-density lipoprotein cholesterol levels 190 mg/dL or greater, and with data on medication use were included. Self-identified race and ethnicity (Asian, Black, Hispanic, and White) and 10-year ASCVD risk category (5%-<7.5%, 7.5%-<20%, ≥20%). Prevalence of statin use, defined as identification of statin use on pill bottle review. A total of 3417 participants representing 39.4 million US adults after applying sampling weights (mean [SD] age, 61.8 [8.0] years; 1289 women [weighted percentage, 37.8%] and 2128 men [weighted percentage, 62.2%]; 329 Asian [weighted percentage, 4.2%], 1032 Black [weighted percentage, 12.7%], 786 Hispanic [weighted percentage, 10.1%], and 1270 White [weighted percentage, 73.0%]) were included. Compared with White participants, statin use was lower in Black and Hispanic participants and comparable among Asian participants in the overall cohort (Asian, 25.5%; Black, 20.0%; Hispanic, 15.4%; White, 27.9%) and within ASCVD risk strata. Within each race and ethnicity group, a graded increase in statin use was observed across increasing ASCVD risk strata. Statin use was low in the highest risk stratum overall with significantly lower rates of use among Black (23.8%; prevalence ratio [PR], 0.90; 95% CI, 0.82-0.98 vs White) and Hispanic participants (23.9%; PR, 0.90; 95% CI, 0.81-0.99 vs White). Among other factors, routine health care access and health insurance were significantly associated with higher statin use in Black, Hispanic, and White adults. Prevalence of statin use did not meaningfully change over time by race and ethnicity or by ASCVD risk stratum. In this study, statin use for primary prevention of ASCVD was low among all race and ethnicity groups regardless of ASCVD risk, with the lowest use occurring among Black and Hispanic adults. Improvements in access to care may promote equitable use of primary prevention statins in Black and Hispanic adults.

Abstract P636: Burden of Atherosclerotic Cardiovascular Disease in Patients With versus Without Cancer: Insights From the Houston Methodist Cardiovascular Disease Learning Health System Registry

Background: Identifying cardiovascular burden in cancer patients is important for appropriate risk stratification. Despite this population-based analyses delineating the burden of cardiovascular disease (CVD) across the spectrum of atherosclerotic CVD (ASCVD) remain less well-established in patients with cancer. We aimed to evaluate and compare the burden of CVD in patients with vs without cancer. Methods: Houston Methodist Learning Health System Registry was utilized to obtain data of ∼1.1 million adult patients reporting in the outpatient department between 2016-2022. All patients with a cancer diagnosis listed on their problems list using the ICD-10 Clinical Modification codes (C00 -C96) were identified. Patients with ASCVD including CAD, PAD, and stroke, HF and AF were also identified using ICD 10-CM. Age-adjusted prevalence and multivariate logistic regression analyses were calculated to determine the burden and odds of CVD in patients with vs without cancer, respectively. Results: A total of 93,238 (8.7%) patients with cancer and 978,301 (91.3%) patients without cancer were included. Age-adjusted burden of ASCVD was higher amongst patients with cancer compared with patients without cancer (9.3 vs 8.2; p&lt;0.01). These results were consistent across the spectrum ASCVD, HF and AF. Multivariate analyses revealed significantly increased odds of ASCVD (OR 1.19 [1.17-1.22]), CAD (OR 1.21 [1.18-1.24]) PAD (OR 1.16 [1.12-1.21]), stroke (OR 1.15 [1.11-1.18]), HF (OR 1.59 [1.56-1.63]) and AF (OR 1.52 [1.49-1.56]) in patients with cancer compared with patients without cancer after adjusting for demographic characteristics. Conclusion: Despite recent therapeutic advancements improving mortality outcomes in patients with cancer, these patients incur a substantial burden of CVD across the spectrum of ASCVD when compared with patients without cancer. Pre-emptive prevention and appropriate risk stratification is important to understand the evolving health care needs of this high cardiovascular risk population.