Risk Factor For Atherosclerotic Disease Research Articles

Lipoprotein (a) Testing in Patients With Atherosclerotic Cardiovascular Disease in 5 Large US Health Systems.

Lipoprotein (a) is an independent risk factor for atherosclerotic cardiovascular disease. However, lipoprotein (a) testing remains variable and it is unclear what factors influence testing and if testing changes clinical management. A retrospective study using electronic medical record data from 5 health systems identified an atherosclerotic cardiovascular disease cohort divided into those with and without a lipoprotein (a) test between 2019 and 2021. Baseline characteristics and lipid-lowering therapy patterns were assessed. Multivariable regression modeling was used to determine factors associated with lipoprotein (a) testing. Among 595 684 patients with atherosclerotic cardiovascular disease, only 2587 (0.4%) were tested for lipoprotein (a). Those who were older or Black individuals were less likely to have lipoprotein (a) testing, while those with familial hypercholesterolemia, ischemic stroke/transient ischemic attack, peripheral artery disease, prior lipid-lowering therapy, or low-density lipoprotein cholesterol ≥130 mg/dL were more likely to be tested. Those with a lipoprotein (a) test, regardless of the lipoprotein (a) value, were more frequently initiated on any statin therapy (30.3% versus 10.6%, P < 0.001), ezetimibe (7.65% versus 0.8%, P < 0.001), or proprotein convertase substilisin/kexin type 9 inhibitor (6.7% versus 0.3%, P < 0.001) compared with those without a test. Those with an elevated lipoprotein (a) level more frequently initiated ezetimibe (11.5% versus 5.9%, P < 0.001) or proprotein convertase substilisin/kexin type 9 inhibitor (10.9% versus 4.8%, P < 0.001). Lipoprotein (a) testing in patients with atherosclerotic cardiovascular disease is infrequent, with evidence of disparities among older or Black individuals. Testing for lipoprotein (a), regardless of level, is associated with greater initiation of any lipid-lowering therapy, while elevated lipoprotein (a) is associated with greater initiation of nonstatin lipid-lowering therapy. There is a critical need for multidisciplinary and inclusive approaches to raise awareness for lipoprotein (a) testing, and its implications on management.

Protocol for a Randomized Controlled Trial on the Development and Effectiveness of an Educational Mobile Application Using an Integrated Change Model to Prevent Atherosclerotic Cardiovascular Disease Risk Factors

Background: An effective approach to preventing cardiovascular issues is the use of mobile health applications to improve modifiable risk factors. This protocol for a randomized controlled trial aims to evaluate the development and effectiveness of an educational mobile app that employs an integrated change model to reduce risk factors for atherosclerotic cardiovascular disease (ASCVD) among individuals aged 20 to 69 years. Methods: This study will be a parallel, randomized, single-blind clinical trial utilizing the randomized block design involving 430 participants. The participants will be divided into a control group receiving standard clinical care and an intervention group receiving standard clinical care along with app-based education, over approximately 6 months. Conclusion: This application has been designed to enhance motivation, awareness, and positive habits to reduce risk factors in individuals at increased risk of ASCVD. Consequently, the results could improve cardiovascular health knowledge, manage biological risk factors, and modify cardiac behaviors through mobile applications. This research is expected to present a promising approach to utilizing mobile apps for managing cardiovascular health and contribute to the growing body of research on digital health interventions.

Individuation of a cut-off value of triglyceride-glucose index for incident diabetes mellitus in patients with essential hypertension.

The prevalence of obesity and diabetes, risk factors for atherosclerotic vascular diseases, is increasing worldwide; therefore, it is desirable to early identify them to reduce cardiovascular events. Thus, we investigated whether the triglyceride-glucose index (TyG index), a new marker of insulin resistance, is associated with incident diabetes in patients with newly diagnosed arterial hypertension. We selected 585 patients with newly diagnosed arterial hypertension referred to our tertiary Clinic of Catanzaro University Hospital for the evaluation of their cardiometabolic risk profile. None of the patients had diabetes mellitus at enrollment and took any drug known to affect glucose metabolism. Patients underwent medical history collection, clinical examination and laboratory tests. The TyG index was calculated as the ln [fasting TG (mg/dl) × FPG (mg/dl)/2], as previously suggested. During the follow-up [mean 8.5years (range 3.1-10.7)], there were 78 new cases of incident diabetes (1.57% patient-year). Patients who developed diabetes mellitus were older and had a higher body mass index (BMI), baseline blood pressure, fasting glucose, insulin, homeostatis model sssessment (HOMA) index, triglyceride, creatinine and hs-CRP mean values, while estimated glomerular filtration rate values were lower. At the Cox regression analysis, covariates significantly associated with incident diabetes were: BMI (HR = 2.842, 95%CI = 2.299-3.514), TyG index (HR = 2.392, 95%CI = 1.745-3.192), age (HR = 1.944, 95%CI = 1.527-2.474), hs-CRP (HR = 1.409, 95%CI = 1.153-1.722), and HOMA (HR = 1.325, 95%CI = 1,079-1.756). The best estimated cut-off value of TyG index in predicting diabetes was 4.71. In addition, we documented a significant relationship between TyG index and HOMA (r = 0.575; p < 0.0001). Present data demonstrate that TyG index, a simple and cost-effective marker of insulin resistance, is useful in predicting incident diabetes in patients with arterial hypertension.

Factors affecting in-hospital clinical outcomes in patients with acute limb ischemia undergoing endovascular therapy or fogarty thrombectomy: a large-scale analysis based on the JROAD-DPC database

Abstract Background The etiology of acute limb ischemia (ALI) involves embolism as well as atherosclerotic thrombosis. Although endovascular therapy (EVT) or Fogarty thrombectomy (Fogarty TE) is the recommended revascularization method for ALI, treatment choice based on patient characteristics remains controversial. Purpose This study aimed to evaluate the differences in clinical outcomes between primary treatments and identify predictive factors affecting clinical outcomes in patients with ALI. Methods This retrospective study used data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database, from April 2012 to March 2020. We analyzed 18,701 patients with ALI and categorized them into medication and invasive treatment groups (EVT alone, Fogarty TE alone, bypass surgery alone, and hybrid treatment). The EVT-alone and Fogarty TE-alone groups were compared after propensity score matching, considering 19 clinically relevant covariates. The primary outcomes were in-hospital mortality, major amputation, and bleeding complications (anemia requiring transfusion or endoscopic hemostasis). The secondary outcomes were major adverse cardiovascular events (myocardial infarction, coronary intervention, heart failure, stroke, and cerebral hemorrhage), major amputation and/or death, hospitalization duration, and total cost during hospitalization. Results The EVT-alone group had more patients at a higher risk of atherosclerotic disease, including peripheral artery disease (PAD), chronic kidney disease (CKD), or hemodialysis. The Fogarty TE-alone group had more patients at a higher risk of embolism, including AF or AFL. After propensity score matching, in-hospital mortality (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.29–1.92, p&amp;lt;.0001), bleeding complications (OR: 1.28, 95% CI: 1.12–1.46, p=0.0002), and major amputation rates (OR: 1.44, 95% CI: 1.17–1.76, p=0.0004) were significantly higher in the EVT-alone group than in the Fogarty TE-alone group. Major amputation and/or death rates and total hospitalization costs were higher in the EVT-alone group than in the Fogarty TE-alone group. In interaction analyses, EVT demonstrated a favorable trend of lower risks of death and/or major amputation in patients with PAD, CKD, and diabetes mellitus (all risk factors for atherosclerotic disease), especially in those with PAD and CKD. Conclusions Fogarty TE may be the preferred primary treatment for patients with ALI, particularly those without PAD or CKD.Study flowchartForest plot analyzing interaction effect

Remnant cholesterol, not LDL cholesterol, explains peripheral artery disease risk conferred by apolipoprotein B: a cohort study

Abstract Background Elevated apolipoprotein B (apoB)-containing lipoproteins (=remnants + low-density lipoproteins [LDL]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied risk of chronic limb-threatening ischemia and myocardial infarction. Methods ApoB, remnant cholesterol, and LDL cholesterol were measured in 93,461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1,207 had PAD, 552 had chronic limb threatening ischemia, and 2,022 had myocardial infarction in the national Danish Patient Registry. Remnant and LDL cholesterol were calculated from a standard-lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25,347 of the individuals. Results were replicated in 302,167 individuals without statin use from the UK Biobank (2004-2010). Results In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% confidence interval: 1.5-2.4) and 1.1 (1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (1.4-2.1) and 0.9 (0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32-100%) and 8% (0-46%), respectively; corresponding results were 63% (30-100%) and 0% (0-33%) for risk of chronic limb-threatening ischemia, and 41% (27-55%) and 54% (38-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. Conclusions PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants, while myocardial infarction risk was explained by both elevated remnants and LDL.

Lipoprotein(a) induces spontaneous aortic dissection via increasing monocyte mediated vascular smooth muscle cell phenotype transformation in human Lp(a) transgenic mice

Abstract Background Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent risk factor of atherosclerotic cardiovascular disease and aortic valve stenosis. Recent studies have reported that high levels of Lp(a) are strongly associated with aortic dissection (AD), independent of other cardiovascular risk factors. However, orthologues of Lp(a) are only found in humans, Old World monkeys, apes, and hedgehogs. The lack of a proper animal model has hindered elucidation of the true pathophysiological mechanisms of Lp(a). Here, we conducted the first humanized Lp(a) transgenic mice experiment to verify the pathological mechanism of Lp(a) in aortic dissection. Methods We conducted ApoE knock out and human ApoA transgenic mice via CRISPR-Cas9 and then crossed with human ApoB transgenic mice to achieve high levels of human-like Lp(a) particles in plasma. Plasma was assayed by ELISA for the concentrations of each lipoprotein. Echocardiography was performed to detect aortic morphology in vivo. Single cell transcriptome analysis was performed on the dissection lesion. Cell interaction was examined in macrophage from Lp(a) transgenic mice and vascular smooth muscle cell (VSMC) coculture system. Result Our results indicate that the concentration of ApoA and ApoB in plasma were increased in transgenic mice fed a chow diet. Low density lipoprotein (LDL) levels were increased and shows that LDL is the major cholesterol carrier in these mice. We were surprised to find that the dissection of the ascending aortic arch could be seen by echocardiography in transgenic mice as early as 2 months, and transgenic mice showed significant increase in aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions, resulting in a survival rate of only 58% after 12 months. Single cell transcriptome analysis revealed that Lp(a) transgene induced the inflammatory response, dedifferentiation and pathological VSMC phenotypical switch, and matrix metalloproteinase expression in macrophages. Monocytes isolated from transgenic mice with elevated Lp(a) remain in a long-lasting primed state, as evidenced by an increased capacity to transmigrate and produce proinflammatory cytokines on stimulation. Monocytes isolated from wild type mice cultured in media with high level Lp(a) for 24h also showed the ability to facilitated cocultured VSMC phenotype transformation, which was reversed by E06, a monoclonal antibody blocking the oxidized phospholipids in Lp(a). Conclusion These findings demonstrate that Lp(a) induces spontaneous aortic dissection via increasing monocyte trafficking to the arterial wall, mediating proinflammatory responses and VSMC phenotype transformation through its OxPL content. The study presents a rodent model of spontaneous aortic dissection and provide a novel mechanism by which Lp(a) mediates aortic dissection.Graphical abstract

Lipoprotein(a) cardiovascular disease risk not captured by low density lipoprotein cholesterol and apolipoprotein B

Abstract Background Elevated lipoprotein(a) affects 1 in 5 individuals and is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis (AVS). However, lipoprotein(a) measurements are not widely implemented in clinical practice. Low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) measurements include contributions from lipoprotein(a), yet whether these measurements can replace measurements of lipoprotein(a) in assessing cardiovascular disease risk from this causal risk factor is unknown. Purpose We tested the hypotheses that lipoprotein(a) risk of ASCVD and AVS is captured by LDL cholesterol or ApoB. Methods We included 70,189 individuals from a prospective contemporary cohort study of the general population. Mediated risk by LDL cholesterol and ApoB in the association between lipoprotein(a) and risk of ASCVD and AVS was examined using four-way decomposition analyses stratified by statin treatment at baseline. Results During a median follow-up of 10.8 years, 7,127 developed ASCVD and 1,516 AVS. Per 50 mg/dL higher lipoprotein(a), multivariable adjusted hazard ratios were 1.22 (95% CI: 1.18-1.26) for ASCVD and 1.36 (1.28-1.46) for AVS. In individuals without statin use, LDL cholesterol mediated 19% (15%-24%) of the risk of ASCVD from lipoprotein(a) and 7.7% (1.5%-14%) of the risk of AVS from lipoprotein(a) (Figure 1). Corresponding values for ApoB were 14.0% (11%-18%) and 6.6% (2.8%-10%). In statin users (n=9,570), LDL cholesterol did not mediate risk of ASCVD from lipoprotein(a) but mediated 8.0% (0.8%-15%) of the risk of AVS from lipoprotein(a). Correspondingly, ApoB mediated 9.8% (2.2%-17%) of the risk of ASCVD and 4.2% (0.4%-8.0%) of the risk of AVS from lipoprotein(a). Conclusion Lipoprotein(a) risk of ASCVD and AVS is not adequately captured by LDL cholesterol and ApoB. Therefore, lipoprotein(a) measurement is needed in all individuals to capture the cardiovascular disease risk from this causal risk factor.

Association of the lipoprotein(a) gene (LPA) p.Ile4399Met variant with lipoprotein(a) level and cardiovascular events in patients following coronary artery bypass grafting under 65 years of age

Abstract Introduction Lipoprotein(a) (Lp[a]), a well-known risk factor for atherosclerotic cardiovascular disease, is largely determined by variation in the Lp(a) gene (LPA) locus encoding apolipoprotein(a). The LPA gene Ile4399Met (rs3798220) variant has been previously reported to have a strong association with the Lp(a) level in patients with coronary artery disease (CAD), however, its prevalence in the middle-age patients after coronary artery bypass grafting (CABG) has not been investigated. Purpose To assess the frequency of the LPA gene c.5673A&amp;gt;G variant (p.Ile4399Met; rs3798220) in Polish patients with CAD following CABG under 65 years of age and determined its association with laboratory and clinical variables. Materials and Methods We studied 215 patients with stable CAD, aged 59.5±4.9 years, who underwent primary and isolated CABG surgery (at age of 57.8±5.4 years), including 195 (90.8%) male. Clinical characteristics and analysis of the LPA c.5673A&amp;gt;G variant were performed. Results The genotype distribution was as follows: AA – 192 (89.3%), AG – 19 (8.8%), and GG – 4 (1.9%). The c.5673G allele carriers had higher Lp(a) level (106.5 [IQR 77.9-149.7] vs 10.4 [IQR 4.4-43.0] mg/dL, p&amp;lt;0.001) compared with non-carriers. Among the c.5673G allele carriers, Lp(a) correlated positively with pack-years of smoking (r=0.563, p=0.045) and fibrinogen (r=0.431, p=0.040), but not with low-density lipoprotein cholesterol (r=0.202, 0.368). There were no other genotype-associated differences with regard to demographic and clinical variable between carriers and non-carriers, including myocardial infarction (56.5% vs 47.9%, p=0.511), peripheral artery disease (21.7% vs 15.1%, p=0.377) and cerebrovascular events (13.0% vs 6.7%, p=0.389). Conclusions To our knowledge, this is the first report on the prevalence of LPA rs3798220 variant in patients with advanced CAD following CABG surgery under 65 years of age. We showed a relatively high (10.7%) percentage of c.5673G allele carriers who have ten times higher Lp(a) levels compared to the wild type, however, its impact on cardiovascular events requires further studies.

SHR-1918, a monoclonal antibody against angiopoietin-like 3, in healthy subjects: a randomized, double-blind, placebo-controlled, phase 1 study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) are important risk factors for atherosclerotic cardiovascular disease. Angiopoietin-like 3 (ANGPTL3) is involved in the regulation of lipid metabolism and can increase serum TG and LDL-C levels by reducing their clearance. SHR-1918 is an ANGPTL3 monoclonal antibody developed to inhibit ANGPTL3 activity, thereby reducing the level of TG and LDL-C. Purpose This phase 1 single ascending dose study aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1918 in healthy subjects. Methods Six dose cohorts were planned, including 100, 300, 450, 750, 900 (optional), and 1200 (optional) mg. For each cohort, 12 healthy subjects were enrolled and randomized (9:3) to receive single subcutaneous SHR-1918 or placebo. Subjects were observed for seven days post-dose and followed up to Day 148 for the 100 mg cohort and Day 190 for the other dose cohorts. The primary endpoints were safety and tolerability. Results A total of 72 subjects were enrolled in the six dose cohorts from 100 to 1200 mg (SHR-1918, n = 54; placebo, n = 18). SHR-1918 was well-tolerated at tested doses. Treatment-emergent adverse events (TEAEs) were reported in 49 (90.7%) subjects in the SHR-1918 group and 17 (94.4%) subjects in the placebo group. The most common TEAEs were upper respiratory tract infection (25.9% with SHR-1918 vs. 27.8% with placebo), protein urine present (22.2% vs. 22.2%), and blood uric acid increased (16.7% vs. 16.7%). All TEAEs were mild or moderate in severity. There were no serious adverse events or TEAEs leading to death. Serum concentration of SHR-1918 generally increased with increasing doses. Maximum serum concentration was reached 8.0 to 10.0 days after injection, and mean t½ was 29.4 to 53.3 days across the dose range. SHR-1918 exposure exhibited in a slightly greater-than-dose-proportional manner from 100 to 1200 mg. Serum LDL-C and TG levels markedly and rapidly decreased in all SHR-1918 dose cohorts and remained under the baseline value up to the end of follow-up period for the higher doses, whereas those in the placebo group were above baseline at most follow-up visits (Figure 1 and 2). In the 750 to 1200 mg cohorts, the largest decline in LDL-C from baseline ranged from -46.5% to -49.1%, and the maximum decrease in TG ranged from -67.4% to -82.8%. On Day 85, there remained to be 36.9% to 39.0% reduction in LDL-C and 59.9% to 79.1% reduction in TG for the higher doses. Anti-drug antibody was not detected in SHR-1918-treated subjects. Conclusions SHR-1918 was well-tolerated and showed promising efficacy in healthy subjects. A phase 2 study has initiated to evaluate SHR-1918 in hyperlipidemic patients (NCT06109831).Serum LDL-C after SHR-1918 injectionSerum TG after SHR-1918 injection

Study of lipoprotein(a) and its impact on atherosclerotic cardiovascular disease: design, rationale, and first results of the Zabrze-Lip(a)R Registry

Abstract Aims Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. Increased Lp(a) concentration &amp;gt;30 mg/dl may cause faster atherosclerosis. There is a need to characterize further the clinical phenotypes in patients at risk for ASVD with high Lp(a) levels. Material The Zabrze-Lip(a)R Registry was created on the basis of data from 2,001 patients with high- and very high cardiovascular risk treated in a tertiary hospital, and the Registry patients will be followed for many years. Mortality and cardiovascular events, such as known death, MI, and stroke, will be assessed. Results The median Lp(a) concentration in the entire population was 6.6 mg/dl (mean 14.3 ± 19.4 mg/dl). Preliminary results of the study group showed that 540 (27%) patients had elevated Lp(a) levels above 30 mg/dl, mainly in patients with established ASCVD after MI and/or coronary revascularization. Patients with elevated Lp(a) levels are older and have higher hematocrit and NT-proBNP and CRP levels. Conclusions Extensive observational studies are essential for further work that objectively collects information on the risks associated with Lp(a) values and cardiovascular disease. Additionally, developing a deeper understanding of the impact of Lp(a) on prognosis will be valuable in how Lp(a) interacts with other established risk factors in improving cardiovascular risk prediction.Distribution of Lp(a) concentrationsComparison of pts with different Lp(a)

Peroxisome proliferator-activated receptor gamma regulates interleukin-6 induced lipoprotein(a) gene expression in human HepG2 cells

Abstract Background Lipoprotein(a)[Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and outcomes. The LPA gene promoter contains an interleukin 6 (IL-6) responsive binding site. IL-6 is a pro-inflammatory cytokine and data from patients with inflammatory diseases indicate an impact of the inflammatory milieu on LPA gene regulation and Lp(a) production. In a clinical study, the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone was associated with decreased Lp(a) levels. Publicly accessible ChIP-sequencing of human hepatocytes and measures of Lp(a) production by HepG2 cells provide an opportunity to explore PPARγ regulation of hepatic Lp(a) production. Purpose To investigate the role of PPARγ as a regulator of hepatic Lp(a) production. Methods Public ChIP-sequencing of human hepatocytes was analyzed. Commercially available HepG2 cells were incubated with one of the following: (1) scrambled small interfering RNA (siRNA) alone (control); (2) IL-6 (20ng/mL) and scrambled siRNA ; (3) IL-6 and PPARγ siRNA ; and (4) IL-6 and pioglitazone (25uM). LPA transcription was measured using the quantitative polymerase chain reaction. Results Analysis of the ChIP-sequencing data demonstrated that the LPA locus variant rs56393506, which is associated with increased Lp(a) levels and ASCVD risk in the general population, was within the location of the PPARγ binding site in the LPA promoter (Figure 1). IL-6 significantly increased LPA transcription in the HepG2 cells, compared to control (1.65±0.44 vs. 0.66±0.45, p=0.0027). In the presence of siRNA-mediated knock-down of PPARγ (58±17% PPARγ reduction, p&amp;lt;0.0001 vs. scrambled control), the effect of IL-6 on LPA transcription was significantly amplified (6.78±2.4 vs. 1.65±0.44, p=0.0009). IL-6 did not increase LPA transcription in the presence of the PPARγ agonist pioglitazone compared to control (0.16±0.03 vs. 0.66+0.45, p=0.11, Figure 2). Conclusion PPARγ is a negative regulator of IL-6 induced hepatic Lp(a) production and may represent a new therapeutic target in patients with inflammatory conditions.Figure 1Figure 2

Factors Associated with Lipoprotein(a) Testing Among Multiethnic Individuals.

Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and clinical guidelines recommend incorporating Lp(a) testing in routine care. Examine real-world, contemporary clinical testing patterns of Lp(a) among multiethnic populations. In this nested case-control study, we assessed the prevalence and factors associated with Lp(a) testing within a large Northern Californian health system between 2010 and 2021. Incident density matching was used to select controls matched with a case for a case:control ratio of up to 1:5. Conditional logistic regression was used to assess the relationship between Lp(a) testing, sociodemographic, and clinical characteristics. We included individuals aged 18years or older with ≥ 2 primary care visits during the study period. Lp(a) testing rates over time and factors associated with testing based on demographic, medical, and healthcare utilization variables. Of the 1,484,410 individuals in the cohort, 14,818 (1.0%) underwent Lp(a) testing. The median Lp(a) level was 35mg/dL and over a third of individuals had Lp(a) levels > 50mg/dL. After adjustment, South Asian individuals were three times more likely to have undergone Lp(a) testing, as compared to non-Hispanic White individuals [OR = 3.19, (95% CI = 2.98, 3.41)], while those identified as non-Hispanic Black and Hispanic were significantly less likely to have undergone Lp(a) testing [OR = 0.70, (95% CI = 0.62, 0.80) and 0.64 (95% CI = 0.59, 0.69), respectively]. Those with a history of ASCVD had over twice the odds of undergoing testing [OR = 2.14 (95% CI = 1.99, 2.29)], as did individuals with more frequent primary care visits [OR = 1.99 (95% CI = 1.84, 2.15)]. Lp(a) testing rates in real-world settings are low, with significant disparities by race, ethnicity, and healthcare utilization. Expanding access to Lp(a) testing may help reduce disparities within ASCVD risk assessment and treatment as new targeted therapeutic agents become available.

Proposing new lipoprotein (a) cut off value for Kazakhstan: pilot study.

There is no consensus on the optimal concentration of lipoprotein(a) (Lp(a)) for the risk of atherosclerotic cardiovascular diseases (ASCVD) and aortic valve stenosis. In various clinical guidelines and agreed documents, the threshold level of Lp (a) is 30 mg/dl or 50 mg/dl. We estimated the cut-off value of Lp (a) associated with the risk of developing various localizations of atherosclerosis for the Central Asia, including Kazakhstani population. This study was conducted at National Research Cardiac Surgery Center, Kazakhstan. 487 patients were included, of which 61.3% were men. The mean age of all participants was 57.3 ± 12.6 years. Bivariate and multivariable logistic regression analysis was used to study the relationship between risk factors and plasma lipoprotein (a) levels. The threshold value of lipoprotein (a) was predicted using the Youden index. For Kazakhstani population the lipoprotein (a) cut offs for the risk of developing atherosclerotic CVD and aortic valve calcification was 21.1 mg/dl (p < 0.05). There was no relationship with the level of lipoprotein (a) and low-density lipoprotein cholesterol (LDL-C), which suggests that lipoprotein (a) is an independent risk factor for the development of ASCVD. This study offers new insights into the threshold value of lipoprotein (a) in Kazakhstan, highlighting its role as a risk factor for atherosclerotic cardiovascular diseases and aortic valve calcification. The findings suggest that the internationally recommended Lp(a) cutoffs may not be suitable for Central Asian populations, as the threshold in our study is significantly lower at 21.2 mg/dL. These results emphasize the need for further research with larger sample sizes to establish more region-specific cutoffs.

7551 Association of Remnant Cholesterol with Sarcopenia in Korean Adults: A Nationwide Population-Based Study using Data from the KNHANES

Abstract Disclosure: S. Jang: None. S. Hwang: None. A. Jang: None. K. Kim: None. J. Yu: None. N. Kim: None. H. Yoo: None. J. Seo: None. S. Kim: None. N. Kim: None. S. Baik: None. K. Choi: None. Objectives: Mounting evidences indicate the importance of interplay between skeletal muscle and lipid metabolism. Remnant cholesterol (remnant-C) is considered as one of the principal residual risk factors for atherosclerotic cardiovascular disease (ASCVD) as well as metabolic disorders, but there is limited study about the impact of remnant-C on sarcopenia. Research design and Methods: Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) between 2008 and 2011 was used in this nationwide population-based study. A total of 17,408 participants were enrolled. Subjects were categorized into 4 groups according to the quartile of remnant-C values. We conducted multivariable logistic regression analysis to evaluate the association between remnant-C and muscle mass measured using dual-energy X-ray absorptiometry (DXA). Results: 1,989 participants (11.4%) presented low muscle mass, and there was a sequential increase in the percentage of low muscle mass across remnant-C quartiles (Q1, 5.8%; Q2, 9.9%; Q3, 12.9%; Q4, 17.1%). In the full adjusted model, those in the highest remnant-C quartile group showed the highest odds ratio for low muscle mass after adjusting for various confounding factors (Q2, 1.18 [0.95-1.47]; Q3, 1.12 [0.9-1.39]; Q4, 1.37 [1.1-1.71], P &amp;lt;0.05). A wide range of subgroup and sensitivity analyses showed consistent results, which may support the robustness of the present findings. Conclusions: Increased remnant-C value is related to high risk of low muscle mass in Korean population. Remnant-C may be a novel marker to predict and manage sarcopenia in the aging society. There should be future research to verify its clinical usefulness. Presentation: 6/2/2024

Elevated Concurrent Carotid Atherosclerosis Rates in Patients with metabolic dysfunction-associated fatty liver disease (MAFLD) Compared to non-alcoholic fatty liver disease (NAFLD): A Cross-sectional Observational Study

Background and AimNon-alcoholic fatty liver disease (NAFLD) has been recognized as an independent risk factor for atherosclerotic cardiovascular disease. Recently, there has been a shift towards diagnosing metabolic dysfunction-associated fatty liver disease (MAFLD), offering simplified criteria and improved risk assessment. However, the association between MAFLD and carotid atherosclerosis remains poorly understood. Methods and ResultsThe study analyzed the association of concurrent carotid atherosclerosis between NAFLD and MAFLD patients with a retrospective cohort design. The study enrolled participants who underwent abdominal and carotid artery ultrasounds from a medical center in Taiwan. NAFLD and MAFLD were diagnosed based on imaging and specific criteria. Associations between NAFLD, MAFLD, and carotid atherosclerosis were analyzed using logistic regression.Among 11,194 participants, 57.1% were diagnosed with fatty liver disease, among which the NAFLD-MAFLD group comprised 4,689 individuals, with 900 in the NAFLD-only group and 669 in the MAFLD-only group. Significant demographic and clinical differences were observed between groups. Logistic regression showed that the MAFLD-NAFLD group and MAFLD-only group had significantly higher odds of concomitant carotid atherosclerosis. Among MAFLD patients, 65.5% had concurrent carotid arteriosclerosis with an odds ratio of 2.35 compared to non-MAFLD patients. The odds ratios for variables in MAFLD patients, such as diabetes mellitus, Fibrosis-4(FIB-4), number of FIB-4 > 1.3, and number of NAFLD fibrosis score > -1.455 were all greater than 2. ConclusionsMAFLD is associated with a higher prevalence of carotid atherosclerosis, compared to NAFLD. This suggests that MAFLD may serve as a significant risk factor for cardiovascular complications.

Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition).

Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts' Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.

Glycaemic control metrics and metabolic dysfunction-associated steatotic liver disease in children and adolescents with type 1 diabetes.

The aim was to examine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a risk factor for atherosclerotic cardiovascular disease, and its association with glycaemic control metrics in children and adolescents with type 1 diabetes (T1D). We enrolled 244 children and adolescents with T1D (115 girls, mean age: 16.2 ± 3.2 years). The diagnosis of MASLD was defined by the presence of hepatic steatosis on ultrasonography in combination with at least one of five common cardiometabolic risk factors. Metrics of short-term and long-term glycaemic control, blood pressure, lipids, anthropometric characteristics and three genetic variants strongly related to MASLD susceptibility (rs738409 [patatin-like phospholipase domain-containing 3], rs58542926 [transmembrane 6 superfamily member 2] and rs1260326 [glucokinase regulator]) were assessed. Characteristics of these subjects with and without MASLD were compared using the unpaired Student t test, Mann-Whitney test or χ2 test as appropriate. Logistic regression analyses were performed to determine the main independent predictors of MASLD. The prevalence of MASLD was 27.5% in children and adolescents with T1D. Blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein cholesterol, HbA1c and time above range (TAR) were significantly higher in subjects with MASLD than in those without MASLD. Mean HbA1c values from diabetes onset (adjusted odds ratio [OR]: 1.703, 95% confidence interval [CI]: 1.040-2.787, p = 0.034), TAR (adjusted OR: 1.028, 95% CI: 1.009-1.047, p = 0.006) and plasma LDL cholesterol (adjusted OR: 1.045, 95% CI: 1.013-1.078, p = 0.004) were independently associated with the presence of MASLD. MASLD is a common condition in children and adolescents with T1D. The mean HbA1c values from diabetes onset, TAR and LDL cholesterol levels were the independent predictors of MASLD.

Neutrophil count as a risk factor for cardiovascular diseases: how can we manage it?

Neutrophils activation plays a pivotal role in the pathogenesis of atherosclerotic plaque formation, progression and rupture. An association between the leukocyte count and the risk of developing myocardial infarction has been well known for many years; however, only recently did Mendelian randomization studies show that a high neutrophil count is a causal risk factor for atherosclerotic cardiovascular disease. On the other hand, experimental studies show that depletion of circulating neutrophils impairs plaque development. Clopidogrel, an antiplatelet agent, is widely used in combination with aspirin to reduce the incidence of ischemic events in patients treated with coronary stenting. Chronic treatment with this drug reduces inflammatory markers and neutrophil numbers, rarely causing severe leukopenia. The purpose of this review is to present recent evidence showing the link between neutrophil number and the development of cardiovascular diseases and to discuss how the clopidogrel-induced reduction in the neutrophil count may be a beneficial off-target effect of this drug.

Plasma atherogenicity index is a powerful indicator for identifying metabolic syndrome in adults with type 2 diabetes mellitus: A cross-sectional study.

Metabolic syndrome (MetS) is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). Elevated triglyceride (TG) levels and decreased high-density lipoprotein levels (HDL-C) are predisposing factors for the development of ASCVD. Evidence on the association between atherosclerotic index of plasma [AIP = log (TG/HDL-C)] and MetS is limited. Our study aimed to investigate the association between AIP and MetS. This is a cross-sectional study that determines the presence of MetS by assessing anthropometric and biochemical parameters. Multivariate log-binomial regression models were used to analyze the relationship between AIP and MetS risk. To further test the stability of the results, we performed sensitivity analyses in young, non-obese, and normal lipid population. Smoothing plots explored the potential nonlinear relationship between the AIP index for MetS and the estimated potential risk threshold. Predictive power of AIP for MetS using respondent operating characteristic (ROC) curves. The prevalence of MetS was 67.35%. Multivariate logistic regression analysis showed an independent and positive association between AIP and MetS (Per 1 SD increase, PR = 1.31, 95% CI: 1.15-1.47). Sensitivity analysis demonstrated the stability of the results. Smoothing plot showed a nonlinear relationship between AIP and MetS, with an inflection point of 0.66. ROC curve analysis, AIP was an accurate indicator for assessing MetS in type 2 diabetics (AUC = 0.840, 95% CI: 0.819-0.862). AIP is a stable and independently powerful predictor of MetS in T2DM patients. AIP can be used as a simple assessment tool for the early detection of MetS and disease management for the prevention of cardiovascular disease.

Association between elevated lipoprotein(a) levels and vulnerability of carotid atherosclerotic plaque: A systematic review

BackgroundThe role of lipoprotein(a) [Lp(a)] as a potential risk factor for atherosclerotic arterial disease has been extensively studied. However, the available data regarding its association with the vulnerability of carotid atherosclerotic plaque is limited. The main objective of the present systematic review was to assess the association between elevated Lp(a) levels and carotid vulnerable plaque features. MethodsThis systematic review adhered to PRISMA guidelines, conducting a comprehensive literature search to identify studies examining the association between Lp(a) levels and vulnerability of carotid atherosclerotic plaque. Experimental or observational studies were eligible, without language, country, or publication type restrictions. ResultsNine studies including 2058 patients were eligible for this systematic review. Five cross-sectional studies, 3 prospective/retrospective cohorts, and 1 subanalysis of a randomized controlled trial were analyzed. Two cross-sectional studies that compared Lp(a) levels between patients with and without vulnerable carotid plaque showed discordant results. Nevertheless, all the studies that evaluated the prevalence or incidence of vulnerable carotid plaque according to Lp(a) levels showed a positive association. Similarly, one study found a significant correlation between vulnerability of carotid plaque and Lp(a) levels. ConclusionAlmost all studies analyzed in the present review showed a positive association between elevated Lp(a) levels and carotid vulnerable plaque features. However, further research is needed to clarify this issue.