High Atherosclerotic Cardiovascular Disease Risk Research Articles

Lipoprotein(a) levels in a population with clinical atherosclerotic cardiovascular disease in the United States: A subanalysis from the Lp(a)HERITAGE study

BackgroundElevated lipoprotein(a) (Lp[a]) is the most common inherited dyslipidemia that is independently and causally associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, data from diverse populations with ASCVD are lacking. ObjectiveTo evaluate Lp(a) levels in a diverse, contemporary United States (US) population with ASCVD, stratified by race, ethnicity, and sex. MethodsLp(a)HERITAGE (NCT03887520) was a multicenter study that estimated the prevalence of elevated Lp(a) in adults (18–80 years) with ASCVD. US participants with Lp(a) measured in nmol/L pre- or post-enrollment were included in this subanalysis. This study was descriptive; therefore, no statistical comparisons were made. ResultsOf all US participants, 14% had an Lp(a) measurement pre-enrollment. This subanalysis included 7,679 US participants with Lp(a) measurements in nmol/L (80.5% White; 66.4% male; mean age 63.8 years [standard deviation ± 9.7]). Median Lp(a) was >2.5-fold higher in Black participants (132.0 nmol/L; interquartile range [IQR],57.1–239.6) vs the overall population (52.1 nmol/L; IQR, 15.7–167.8), and higher in females compared with males (69.4 nmol/L; IQR, 20.1–194.7 vs 45.6 nmol/L; IQR,14.0–152.6, respectively). Lp(a) levels ≥125 nmol/L were more prevalent among Black (52.0%) and female (38.9%) participants vs the overall population (33.3%). ConclusionsIn US Lp(a)HERITAGE participants, only 14% had an Lp(a) measurement pre-enrollment, despite having ASCVD. One-third of participants demonstrated Lp(a) levels ≥125 nmol/L, the threshold for high ASCVD risk, which was higher among Black (1/2) and female (2/5) participants, suggesting a greater need for Lp(a) testing in these groups to inform ASCVD risk mitigation.

Sex-specific associations of cigarettes and e-cigarettes use with self-reported premature atherosclerotic cardiovascular disease among adults aged 18–54 in the United States

BackgroundPremature atherosclerotic cardiovascular disease (ASCVD) is increasing in young adults (<55 years old). While research suggests females who smoke cigarettes have a higher risk of ASCVD than males, studies on the impact of exclusive e-cigarette and dual use on premature ASCVD are limited. This study investigated the association between tobacco use and self-reported premature ASCVD and explored potential sex differences. MethodsUsing pooled data from 480,317 adults (ages 18–54; ∼50 % female) from the 2020–2022 Behavioral Risk Factor Surveillance System from the United States, logistic regression models assessed associations between cigarette and e-cigarette use patterns and self-reported premature ASCVD. Tobacco use categories were defined as: non-use, former use (cigarettes, e-cigarettes), and current use (cigarettes, e-cigarettes) and dual use. Self-reported premature ASCVD was defined as self-reported angina or coronary heart disease, heart attack, or stroke. Weighted analyses were conducted for the overall sample and stratified by sex. ResultsAfter controlling for potential confounders, former exclusive cigarette (adjusted OR: 1.47 [95 % CI 1.29, 1.67]), current exclusive cigarette (1.68 [1.47–1.94]) and current dual (2.03 [1.69–2.44]) use were associated with higher odds of self-reported premature ASCVD. There was no significant association for e-cigarette use. Sex-specific analyses revealed similar patterns but the magnitude of these associations varied between males and females. ConclusionBoth sexes showed higher odds of self-reported premature ASCVD for dual and exclusive cigarette use. Although the cross-sectional design precludes causal inferences, the findings suggest comprehensive tobacco cessation programs tailored to diverse use patterns are needed to reduce the burden of premature ASCVD.

Abstract 4137570: Atherosclerotic Cardiovascular Disease Risks in Children: An electronic health record data analytics approach

Background and Aims: There is little data on atherosclerotic cardiovascular disease (ASCVD) risk conditions, factors, and tiers in the pediatric population. This study aimed to develop and validate electronic health record (EHR) data analytic algorithms to attain the prevalence of 24 risk conditions, 7 factors, and 4 tiers in children in a rural community. Methods: This study included all the 495,902 subjects from 0 to 18 years at the Geisinger Medical Center from 2004 to 2022. The demographic and clinical data were collected using ICD-10 codes, clinical and laboratory data, and a dual-coded computational algorithm was developed based on the AHA guideline to derive the ASCVD risk conditions, factors, and tiers. To validate the EHR algorithms, the algorithm (rater 1) and a clinician (rater 2) extracted and analyzed the data from 40 randomly selected subjects from this cohort. Kendall’s coefficient of concordance (W) and Gwet’s agreement coefficient were used to evaluate algorithm and clinician agreement within the ASCVD tiers, conditions and factors, respectively. Results: High concordance was observed between algorithmic and clinician raters for risk tiers (W=80%), conditions (80-97%), and factors (49% for blood pressure, and 92% to 97% for the rest of the risk factors). In this cohort, the median age was 3.9 years, 51.0% were male, 80.6% were Non-Hispanic/Latino, and 88.1% were White. Overall, 15.5% (N = 76,945) were at-risk, 7.0% (N = 34,530) at moderate risk, and 4.2% (N = 20,761) at high risk for ASCVD, respectively. The most prevalent risk conditions were obesity (9.1%, N = 45,074), chronic inflammatory conditions (6.8%, N = 33,685), severe obesity (2.7%, N = 13,442), insulin resistance with comorbidities (2.7%, N = 13,397), and hypertension (2.1%, N = 10,436). The most prevalent risk factors were elevated BMI (27.4%, N = 135,904), blood pressure (12.5%, N = 62,015), and fasting lipid profile (8.7%, N = 43,100). Conclusion: Our EHR data analytics algorithm is in high agreement with the clinician rater. The high, moderate, and at-risk ASCVD risk tiers are prevalent in a large contemporary pediatric cohort at Geisinger. Both ASCVD risk conditions and factors are also prevalent, especially obesity, diabetes, hypertension, and hyperlipidemia. These findings suggest the further application and refinement of these algorithms to design innovative approaches for ASCVD risk reduction and prevention in children.

Abstract 4131951: The Safety Profile Of Inclisiran In Patients With Dyslipidemia And Intermediate To High Atherosclerotic Cardiovascular Disease Risk: A Systematic Review And Meta-Analysis

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, thereby improving the clearance of low-density lipoprotein (LDL) cholesterol from the bloodstream. It is given through subcutaneous injections at specified intervals and significantly reduces LDL cholesterol levels in patients with dyslipidemia and with intermediate to high risk of atherosclerotic cardiovascular disease (ASCVD). Goal: We aim to evaluate the safety of the use of inclisiran in patients with dyslipidemia and intermediate to high ASCVD risk. Methods: Three electronic databases of MEDLINE, Web of Science, and Embase were searched from inception to May 5th 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of inclisiran versus the control group . The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events (MACE), injection-site reaction and all treatment-emergent adverse events (TEAE). The effect estimates of outcomes were assessed using risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method given the inter-study variance was inevitable. The subgroup analysis was performed based on different dosing regimens. Results: We included 7 RCTs enrolling 4790 patients (63.8 ± 9.7 years, 66.8 % males) who received inclisiran. Compared to the control group, the use of inclisiran did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I 2 = 0%), MACE (RR, 0.98; 95% CI, 0.82 to 1.17; I 2 = 0%), and TEAE (RR, 1.76; 95% CI, 0.74 to 4.15; I 2 = 74%). However, inclisiran use significantly increased injection-site reaction (RR, 7.08; 95% CI, 3.42 to 14.64; I 2 = 27%). Results are illustrated in the accompanying figure. Conclusions: Inclisiran use significantly increased injection-site reaction, with no increase in mortality and TEAE. Further trials are required to comprehensively assess the safety of inclisiran in the management of dyslipidemia in patients with ASCVD risk.

Danggui Liuhuang Decoction Ameliorates Endothelial Dysfunction by Inhibiting the JAK2/STAT3 Mediated Inflammation

Ethnopharmacological relevanceVascular endothelial dysfunction (VED) is recognized as a key triggering diabetic vascular complications. Danggui Liuhuang Decoction (DGLHD) has shown potential in mitigating these complications. However, the clinical efficacy of DGLHD in enhancing endothelial function, as well as the molecular mechanisms underlying its alleviation of Type 2 Diabetes-Related Vascular Endothelial Dysfunction (T2DM-VED), remains insufficiently understood. Aim of the studyThis study aims to validate the therapeutic efficacy of DGLHD in ameliorating T2DM-VED through clinical research. Furthermore it seeks to analyze the pharmacodynamic basis and molecular mechanisms of DGLHD, elucidating the biological processes through which DGLHD alleviates VED in type 2 diabetes mellitus (T2DM). Materials and methodsPatients diagnosed with "Yin deficiency with hyperactive fire syndrome", who are at a high risk for atherosclerotic cardiovascular disease (ASCVD) associated with T2DM, were recruited for this study. The effect of DGLHD on vascular endothelial function in T2DM was assessed by measuring the levels of pro-inflammatory factors through enzyme-linked immunosorbent assay (ELISA) and flow-mediated dilation (FMD). The primary components of DGLHD were analyzed using the UHPLC-Q-Exactive Orbitrap system. Potential therapeutic targets of DGLHD were predicted using network pharmacology and molecular docking analysis. To validate the mechanism of DGLHD on T2DM-VED, endothelial injury and inflammation cell models were established using human umbilical vein endothelial cells (HUVECs). A mouse model of diabetic endothelial injury was also developed to observe the effects of DGLHD on pro-inflammatory factors and vascular endothelial factors were observed through immunohistochemistry. Additionally, the effects on the JAK2/STAT3 signaling pathway were observed through Western blot experiments. ResultsDGLHD was found to contain 201 active components. Network pharmacology analysis indicated that the treatment of T2DM-VED with DGLHD is associated with modulation of the JAK2/STAT3 signaling pathway. Molecular docking analysis demonstrated that small molecules in DGLHD interact with JAK2 and STAT3. Our clinical study demonstrated that DGLHD significantly reduces the levels of pro-inflammatory factors and improves FMD readings in diabetic patients, thereby alleviating T2DM-VED. DGLHD was shown to inhibit the phosphorylation of JAK2 and STAT3, which blocks the JAK2/STAT3 signaling pathway transmission, reducing the release of pro-inflammatory and vascular endothelial growth factors, and preventing the inflammatory response in vivo and in vitro. ConclusionThis study demonstrates the potential efficacy of DGLHD in improving endothelial function in T2DM patients at high risk for ASCVD. By inhibiting the JAK2/STAT3 signaling pathway, DGLHD effectively reduces the release of pro-inflammatory factors and vascular endothelial growth factors, alleviating VED.

Waist-to-hip ratio as a contributor associated with higher atherosclerotic cardiovascular disease risk assessment in patients with diabetes: a cross-sectional study

IntroductionThis study aimed to identify the factors most strongly associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk score in patients with type 2 diabetes (T2D).MethodsThis cross-sectional study included 4698 patients with T2D over an 11-year period (2010–2021). Patients were categorized into four groups based on their 10-year ASCVD risk score (< 5%, 5–7.5%, 7.5–20%, and > 20%). Multinominal regression analysis was used to evaluate the association between various modifiable and non-modifiable risk factors and the ASCVD risk score.ResultsOf the patients, 35.9% had a 10-year ASCVD risk score below 5%, 12.6% had a score between 5% and 7.5%, 30.8% had a score between 7.5% and 20%, and 19.7% had a score above 20%. Higher ASCVD risk scores were significantly associated with elevated waist-to-hip ratio (WHR > 0.93), pulse pressure, uric acid, triglycerides, and decreased glomerular filtration rate (all p-values < 0.05). WHR demonstrated the strongest association with higher ASCVD risk scores (OR: 4.55, 95% CI: 2.94–7.03, p < 0.001) when comparing patients with ASCVD scores > 5% to those with scores < 5%.ConclusionWHR was independently associated with higher ASCVD risk scores in patients with T2D. Incorporating WHR, along with traditional risk factors, could improve ASCVD risk assessments in this population.

Assessment of lipid profile and its correlation with ASCVD risk in the general population

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major global health issue with high morbidity, mortality, and healthcare costs, emphasizing the need for effective risk assessment for prevention and management. This study aimed to assess the lipid profile of the general population and establish correlations with their ASCVD risk. Methods: This cross-sectional study was conducted among the general population in India. Participants were invited through advertisements to attend the ASCVD camp for a lipid profile check-up. Results: A total of 1068 participants were included, with a mean age of 52.7 years. The majority of participants were male (69.8%). Approximately 33% of participants had low ASCVD risk, followed by 31.6% with high risk, and 26.7% with intermediate risk. In the high ASCVD risk group, participants aged ≥60 years were significantly higher compared to those in the low risk, borderline risk and intermediate risk groups (P&lt;0.001). The mean total cholesterol and low-density lipoprotein (LDL) were significantly increased in participants with high ASCVD risk compared to intermediate, borderline and low risk (P&lt;0.001 and P=0.001). The mean HDL cholesterol level was significantly lower in male participants compared to female participants (P&lt;0.001). There was a positive correlation between age (r=0.783), total cholesterol (r=0.372) and the ASCVD risk score (P&lt;0.001 for both). There was negative correlation between HDL and ASCVD risk score (r=-124; P&lt;0.001). Conclusion: This study demonstrates a significant association between lipid profiles and ASCVD risk. Age, total cholesterol, and LDL levels are positively correlated with ASCVD risk, while HDL levels show a negative correlation.

Physician disagreement with treatment guidelines as a critical barrier to achieving low-density lipoprotein cholesterol targets in very high-risk patients: an implementation science study

Abstract Background/Introduction The challenges that physicians face in implementing evidence-based lipid-lowering therapy in patients at high risk of atherosclerotic cardiovascular disease (ASCVD) are relatively undocumented. Purpose This study aimed to provide insights into the challenges that Korean physicians face in assisting their high-risk ASCVD patients in achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels. Methods We enrolled 704 patients from 10 tertiary hospitals in South Korea, between November 2020 and November 2022. These patients were at very high risk of ASCVD, with baseline LDL-C levels ≥70mg/dL (1.8 mmol/L) while receiving maximally tolerated statins and/or ezetimibe. We measured the proportion of participants achieving LDL-C levels &amp;lt;70mg/dL at visit 1(0)/ visit 2(6-16)/ visit 3 (18-30 weeks), and recorded physician feedback on lipid-lowering treatment strategies. Results Out of the 704 enrolled patients (mean [IQR] age, 66.0 [59–72] years; 580 men [82.4%]), the median (IQR) baseline LDL-C level was 82.0 (74.0–94.5) mg/dL. Lipid-lowering therapy at baseline included statins in 99.0% (with 1.0% statin intolerant) or statins and ezetimibe in 56.4%. The proportion of participants achieving LDL-C levels &amp;lt;70mg/dL at each visit were 0%, 56.3%, and 58.7%, respectively. Among 307 patients on maximally tolerated statins at baseline, physicians did not have an intention to intensify the lipid-lowering treatment regimen in 171 (55.7%) of those patients. (Figure 1) Physician disagreement with the guidelines was the major reason for not using the recommended therapy (70.8%), followed by the patient’s refusal for reasons other than the cost (8.2%), medical limitations such as comorbidities (7.0%), and drug costs (6.4%). Among 397 patients on maximally tolerated statins and ezetimibe at baseline, physicians did not have an intention to intensify the lipid-lowering treatment regimen in 299 (75.3%) of those patients. (Figure 2) Physician disagreement with the guidelines was the major reason for not using the recommended therapy (46.2%), followed by the patient’s refusal for reasons other than the cost (15.7%), medical limitations such as comorbidities (14.4%), and drug costs (12.7%). Conclusion In this implementation science study, the proportion of patients at very high risk of ASCVD who achieved LDL-C levels &amp;lt;70mg/dL via lipid-lowering therapy was less than 60%. Physician disagreement with the guidelines was the main reason for not adopting the recommended intensified LDL-C lowering therapy.Figure 1Figure 2

Red cell distribution width as a predictor of cardiovascular events in high-risk patients with statin intolerance: post-hoc analysis of the CLEAR Outcomes trial

Abstract Background Despite optimal lipid-lowering therapy there is up to 70% residual risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events, motivating further testing of alternative risk factors and disease pathways. Red cell distribution width (RDW) is a simple and reproducible marker of heterogeneity of cell size in the peripheral blood. High RDW is associated with an increased risk of ASCVD and death, independent of established risk factors. Recent data suggest no significant impact of PCSK9 inhibitors on hsCRP or RDW. In CLEAR Outcomes, baseline hsCRP predicted risk for future cardiovascular (CV) events and death more strongly than elevated LDL-C. It has been shown that bempedoic acid (BA) reduces hsCRP, but its effects on RDW are unknown. Purpose To analyze the effect of BA on a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death (MACE-4) and for CV death by baseline RDW, and to confirm the association of increased RDW with elevated risk of MACE. Methods A total of 13,970 individuals with statin intolerance, with or at high risk for ASCVD, were randomized in the multinational CLEAR Outcomes trial with a median follow up of 3.4 years. Compared to placebo, BA reduced mean LDL-C by 21% and median hsCRP by 22% at 6 months. Quartiles of increasing baseline RDW were assessed as predictors of future adverse events after adjustment for traditional risk factors, hsCRP, and randomized treatment assignment. Results Compared to placebo, BA reduced mean RDW by 0.28% at 6 months and 0.13% at 36 months (p&amp;lt;0.0001). There was a weak positive correlation between hsCRP and RDW at baseline (Figure 1). In the placebo group, higher baseline RDW was associated with an increase in the likelihood of MACE-4 and CV death, and the hazard ratios (HR) associated with a 1% increase in RDW after adjusting for covariates and hsCRP were 1.06 (95% CI 1.02-1.11) and 1.22 (1.15-1.29), respectively. When grouped by quartiles of baseline RDW, compared with a reference group with lowest RDW (&amp;lt;13.7%), there was a notable increase in the risk of MACE-4 and CV death among the higher quartiles in the placebo group (Table 1). Those in the 4th quartile demonstrated a 3-fold increase in the risk of CV death (HR, 3.03, 2.00-4.60). The adjusted HRs (95% CI) for BA vs placebo for MACE-4 were generally lower in individuals with elevated baseline RDW than in those in the first quartile [Q1: RDW≤13.7%; 0.96 (0.79-1.17), Q2: RDW 13.7%-14.4%; 0.81 (0.67-0.97), Q3: RDW 14.4%-15.2%; 0.90 (0.75-1.09), and Q4: RDW&amp;gt;15.2%; 0.84 (0.7-1.01)]. Conclusions In a large randomized controlled clinical trial setting, we confirmed an association between elevated RDW and MACE-4. Compared with placebo, BA demonstrated efficacy in reducing CV risk in patients with moderately increased RDW.Figure 1.Correlation of hsCRP and RDWTable 1.Risk of Outcome by RDW Quartile

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.

Serum lipid profiles and uptake of lipid-lowering therapy in patients with premature atherosclerotic cardiovascular disease (ASCVD) in comparison to older patients with ASCVD

Abstract Background Serum lipid levels are well-established risk factors for developing atherosclerotic cardiovascular disease (ASCVD). There are multiple guideline-supported treatments for managing dyslipidaemia for secondary prevention of ASCVD events. Lipid profiles and uptake of guideline-directed lipid-lowering therapy (GDLLT) is poorly characterised in patients with premature ASCVD compared to their older counterparts. Purpose To investigate serum lipid profiles and GDLLT uptake in patients with premature ASCVD in comparison to older patients with ASCVD. Methods Consecutive patients who underwent inpatient invasive coronary angiography at our institution between January 2019-December 2021 were examined. Patients with confirmed ASCVD on coronary angiography were stratified into two groups based on the 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias definition of premature ASCVD: Group 1 comprised of younger patients (&amp;lt;55 years for men, &amp;lt;60 years for women) and Group 2 comprised of older patients (≥55 years for men, ≥60 years for women). Demographics, clinical and biochemical parameters (including lipid profiles) and medications were obtained from the electronic medical record and compared between groups to identify differences in risk factor profiles. Results A total of 1437 patients (980 [68.2%] male, mean age 62.4±13.9 years) underwent coronary angiography. 916 patients (63.7%) had confirmed ASCVD, of which 225 were classified as premature ASCVD (24.6%, mean age 47.8±10.1 years) vs 691 older patients with ASCVD (75.4%, mean age 69.5±8.7 years). Group 1 patients had significantly higher mean BMI (31.7±8.1 vs 69.5±8.7; p=0.001) and lower prevalence of hypertension (54.2% vs 69.5%; p&amp;lt;0.001) or chronic kidney disease (5.3% vs 12.6%; p=0.002) compared to Group 2. There were no significant differences in sex, diabetes mellitus, or smoking history. Lipid profiles were significantly different between the two groups: Group 1 had higher levels of total cholesterol (TC), LDL-C, triglycerides, and TC/HDL-C ratio, but lower HDL-C levels (all p&amp;lt;0.001). A lower proportion of Group 1 patients were on GDLLT (42.7% vs. 60.3%; p&amp;lt;0.001). Amongst patients on GDLLT, there were similar rates in the use of high-intensity statins between groups, but Group 1 patients were significantly more likely to have an LDL-C level ≥1.8mmol/L (p=0.003). Multivariable models for individual lipid subfractions, accounting for gender, cardiovascular risk factors, and LLT use, showed that all lipid parameters remained significantly different between groups (all p&amp;lt;0.001). Conclusion Patients with premature ASCVD have significantly different lipid profiles compared to older ASCVD patients. They also have lower uptake of guideline-directed LLT and are less likely to meet recommended LDL-C targets for high-risk ASCVD despite therapy. These findings highlight the need for tailored risk factor evaluation and management in this population.

Risk-enhancing factors and social determinants of health in risk assessment for atherosclerotic cardiovascular disease.

The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70-189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment.

Challenge of cardiovascular prevention in primary care: achievement of lifestyle, blood pressure, lipids and diabetes targets for primary prevention in England – results from ASPIRE-3-PREVENT cross-sectional survey

BackgroundImplementation of the cardiovascular disease (CVD) prevention guidelines in the UK has been repeatedly evaluated under the auspices of the British Cardiovascular Society in three Action on Secondary and Primary...

Serum Lipoprotein(a) Levels and Their Association with Atherosclerotic Cardiovascular Disease in Japan.

To investigate the distribution of lipoprotein(a) (Lp(a)) and its association with atherosclerotic cardiovascular disease (ASCVD) in Japanese patients at high risk for ASCVD using a health insurance database. Between July 2013 and June 2021, patients eligible for ASCVD prevention according to the 2017 Japan Atherosclerosis Society (JAS) guidelines with documented Lp(a) test results were extracted from the Medical Data Vision claims database and divided into three groups: primary prevention high-risk (Group I), secondary prevention (Group II) and secondary prevention high-risk (Group III). Data on lipid levels, cardiovascular morbidity risk factors and lipid-lowering treatments were extracted. Of 700,580 patients with documented low-density lipoprotein cholesterol (LDL-C), 2,967 (0.42%) were tested for Lp(a). In 2,170 eligible patients, the median [interquartile range] serum concentration of Lp(a) was 13.9 [7.5-24.6] mg/dL, with 151 patients (7.0%) above the recommended risk threshold of ≥ 50 mg/dL. Lp(a) levels increased with risk across all prevention groups. Being in the highest Lp(a) quintile (Q5) was associated with an increased frequency of ASCVD (28.9% versus 18.9% in the lowest quintile (Q1) for unstable angina; 18.7% versus 10.1% for myocardial infarction; 27.9% versus 17.0% for ischemic stroke). In the secondary prevention groups, the proportion of patients meeting an LDL-C target of ＜70 mg/dL decreased from 30.2% in Q1 to 19.0% in Q5 for Group II and from 32.9% to 16.3% for Group III. Despite a high prevalence of Lp(a) ≥ 50mg/dL in Japanese patients at high risk for ASCVD, it found that the Lp(a) testing rate was very low.

Evaluating the atherosclerosis cardiovascular disease risk score in patients with brain metastases: Associations with overall survival and high-value care outcomes

ObjectiveBrain metastases (BM) constitute the most common intracranial tumor in adults. Prior literature indicates the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score is associated with increased risk of cancer, potentially attributable to shared risk factors. Understanding the role of ASCVD risk scores in BM may help optimize their care and inform clinical decision-making. Our aim was to explore associations between ASCVD risk score in BM patients and their overall survival, hospital charges, and non-routine discharge disposition. MethodsElectronic medical records were reviewed to collect clinical data for BM patients undergoing surgery at a single institution (2017–2021). Regression analyses were performed accordingly and maximally selected rank statistics were employed to identify an optimal cutoff for ASCVD risk scores. The random survival forest (RSF) machine learning technique identified the most important variable associated with survival outcomes in BM patients. ResultsA total of 139 patients were included with average age 62.93±9.29 years, 48.2 % male, 25.2 % with high hospital charges, and 23.7 % experiencing non-routine discharge. Among these patients, 32.3 % had prior history of an ASCVD event, while 67.7 % did not. Overall, this cohort had an average 10-year ASCVD risk score of 12.51±12.98, indicating intermediate risk of ASCVD among all BM patients. On multivariate logistic regression, prior history of ASCVD was associated with higher odds of high hospital charges (OR=3.670, p=0.018), and higher ASCVD risk scores were associated with greater odds of non-routine discharge (OR=1.059, p=0.012). On the multivariate Cox regression model, higher ASCVD risk scores correlated with worse overall survival (HR=1.031, p=0.014). A threshold of 25.1 was identified for high-risk ASCVD scores. Patients with ASCVD scores >25.1 exhibited reduced overall survival in Kaplan-Meier analysis (p=0.015) and multivariate Cox regression (HR: 2.811, p=0.016). Notably, ASCVD risk scores were found to be the most important variable in predicting worse survival outcomes in BM patients compared to other established frailty indices. ConclusionThis study indicates higher ASCVD risk scores in BM patients are associated with worse overall survival. Integrating ASCVD assessment into clinical workflow may facilitate more informed risk-based decision-making.

Efficacy of Traditional Anti-lipidemic Drugs in Lowering Lipoprotein(a) Levels: A Systematic Review.

Lipoprotein(a), or Lp(a), was identified in the early 1960.Its role as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) became widely recognized by the late 20th century, regardless of other traditional risk markers such as low-density lipoproteins and high-density lipoproteins. This study aimed to systematically review available literature and compare the efficacy of different lipid-lowering drugs, both approved for clinical use and currently undergoing trials, in lowering Lp(a) levels. A comprehensive search of medical databases including PubMed, PubMed Central (PMC), Medline, ScienceDirect, Cochrane Library, and Google Scholar was conducted to identify relevant studies. A total of 29 research papers met the inclusion criteria, focusing on the impact of various lipid-lowering drugs on Lp(a) concentration in patients with significantly elevated baseline Lp(a) levels. Plasma Lp(a) levels exceeding 30 mg/dL are associated with a higher risk of ASCVD, including myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and increased all-cause mortality. Most commonly used lipid-lowering agents, such as statins, fibrates, ezetimibe, and nutraceuticals like coenzyme Q10 (CoQ10), showed no significant effect on Lp(a) plasma levels. However, Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were found to effectively reduce plasma Lp(a) concentrations. Emerging therapies targeting apolipoprotein(a) RNA, including anti-sense oligonucleotides (ASO) and small interfering RNA (siRNA), significantly reduced Lp(a) levels in Phase 2 trials. While several lipid-lowering agents have minimal impact on Lp(a) levels, therapies like Lp(a) apheresis, PCSK-9 inhibitors, and novel RNA-targeting drugs show promise in effectively reducing Lp(a) concentrations. However, whether these reductions translate into decreased cardiovascular events remains to be determined.

LIpid Response to Statins ± Ezetimibe In Mumbai (LIRIM): A Cross-sectional Observational Study.

India has the highest burden of cardiovascular disease (CVD) among developing nations. Data from international studies show significant underimplementation of recommended aggressive lipid-lowering strategies for achieving low-density lipoprotein cholesterol (LDL-C) goals, especially after percutaneous coronary intervention (PCI), a pattern also observed in India. Moreover, ethnic variation in response to statin therapy has prompted clinicians to adopt lower doses of statin therapy in Asians to achieve comparable LDL-C lowering. To document the dose of statin ± ezetimibe required to achieve the European Society of Cardiology (ESC) goals of LDL-C <55 mg/dL in Indian patients with established atherosclerotic cardiovascular disease (ASCVD). This retrospective single-center, cross-sectional, observational, all-comers study in Mumbai evaluated the dose of atorvastatin (A)/rosuvastatin (R) ± ezetimibe (E) treatment at which patients with established ASCVD (n = 542), irrespective of their baseline level, achieved LDL-C goals (<55 mg/dL). Those with LDL-C levels >55 mg/dL on current therapy were switched to R 40 mg ± E 10 mg daily. The final data set (n = 340) included those who achieved LDL-C goals at the initial visit and those at follow-up. The primary and secondary outcomes assessed the impact of R 40 mg ± E 10 mg (R40 ± E10) on LDL-C (<55 mg/dL) and non-high-density lipoprotein cholesterol [non-HDL-C (<85 mg/dL)] goal achievement, respectively. At the end of follow-up, LDL-C <55 mg/dL was observed in 42.16% of patients (n = 113) with R40 and in another 43.28% (n = 116) with R40 + E10. A few patients (n = 39; 14.6%) achieved this goal with other dosages. Similarly, non-HDL-C <85 mg/dL was observed in 39.3% of patients (n = 107) with R40 and in another 47.4% of patients (n = 129) with R40 + E10. Overall, around 20% of patients were unable to achieve their LDL-C and non-HDL-C goals despite being on high-intensity statin ± E therapy. In the first report of its kind in India, this study showed that suboptimal LDL-C goal achievement occurred in around 20% of high-risk ASCVD patients on dual therapy. This indicates that clinicians should consider the addition of other therapies [e.g., bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and inclisiran] to mitigate the residual risk. Several more trials are needed to determine the most suitable treatment regimen for this population.

Progression of Coronary Artery Calcification and Risk of Clinical Events in CKD: The Chronic Renal Insufficiency Cohort Study

Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD. Prospective cohort study. & Participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least one CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time. Observed or imputed CAC progression, categorized as incident CAC among participants with zero CAC on the baseline scan, or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC ≥50 Agatston units per year. Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality. Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline. A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 (32.5%) participants without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a ≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% confidence interval [CI]: 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI: 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (hazard ratio [HR]: 1.42; 95% CI: 0.85-2.35) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI: 1.31-2.28). Progressive CAC was not associated with incident heart failure. Residual confounding and limited statistical power for some outcomes. Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline.

Low-Density Lipoprotein Cholesterol, Cardiovascular Disease Risk, and Mortality in China

Limited evidence supports the association between low-density lipoprotein cholesterol (LDL-C) and mortality across different atherosclerotic cardiovascular disease (ASCVD) risk stratifications. To explore the associations between LDL-C levels and mortality and to identify the optimal ranges of LDL-C with the lowest risk of mortality in populations with diverse ASCVD risk profiles. The ChinaHEART project is a prospective cohort study that recruited residents aged 35 to 75 years from 31 provinces in mainland China between November 2014 and December 2022. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts on the basis of their medical history and ASCVD risk. Data analysis was performed from December 2022 to October 2023. The primary end point was all-cause mortality, and secondary end points included cause-specific mortality. Mortality data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed by using Cox proportional hazard regression models with various adjusted variables. A total of 4 379 252 individuals were recruited, and 3 789 025 (2 271 699 women [60.0%]; mean [SD] age, 56.1 [10.0] years) were included in the current study. The median (IQR) LDL-C concentration was 93.1 (70.9-117.3) mg/dL overall at baseline. During a median (IQR) follow-up of 4.6 (3.1-5.8) years, 92 888 deaths were recorded, including 38 627 cardiovascular deaths. The association between LDL-C concentration and all-cause or cardiovascular disease (CVD) mortality was U-shaped in both the low-risk cohort (2 838 354 participants) and the primary prevention cohort (829 567 participants), whereas it was J-shaped in the secondary prevention cohort (121 104 participants). The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C concentration associated with the lowest all-cause mortality (90.9 mg/dL vs 117.0 mg/dL) and CVD mortality (87 mg/dL vs 114.6 mg/dL) were both lower in individuals with diabetes than in individuals without diabetes in the overall cohort. This study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes.

A significant presence in atherosclerotic cardiovascular disease: Remnant cholesterol: A review.

The current first-line treatment for atherosclerotic cardiovascular disease (ASCVD) involves the reduction of a patient's low-density lipoprotein cholesterol (LDL-C) levels through the use of lipid-lowering drugs. However, even when other risk factors such as hypertension and diabetes are effectively managed, there remains a residual cardiovascular risk in these patients despite achieving target LDL-C levels with statins and new lipid-lowering medications. This risk was previously believed to be associated with lipid components other than LDL, such as triglycerides. However, recent studies have unveiled the crucial role of remnant cholesterol (RC) in atherosclerosis, not just triglycerides. The metabolized product of triglyceride-rich lipoproteins is referred to as triglyceride-rich remnant lipoprotein particles, and its cholesterol component is known as RC. Numerous pieces of evidence from epidemiological investigations and genetic studies demonstrate that RC plays a significant role in predicting the incidence of ASCVD. As a novel marker for atherosclerosis prediction, when LDL-C is appropriately controlled, RC should be prioritized for attention and intervention among individuals at high risk of ASCVD. Therefore, reducing RC levels through the use of various lipid-lowering drugs may yield long-term benefits. Nevertheless, routine testing of RC in clinical practice remains controversial, necessitating further research on the treatment of elevated RC levels to evaluate the advantages of reducing RC in patients at high risk of ASCVD.