Cholesterol-lowering Medications Research Articles

#843 Methylation of HMGCR gene promoter in patients on hemodialysis

Abstract Background and Aims Patients with chronic kidney disease (CKD) exhibit a pronounced risk for cardiovascular mortality; the most vulnerable group enrolls patients on hemodialysis. Unfortunately no meaningful decrease of cardiovascular risk after cholesterol lowering medication – inhibitors of HMGCR - was demonstrated in hemodialysed patients. The incidence of complications in CKD patients correlates with changed epigenetic mechanisms, the most studied epigenetic phenomenon is DNA methylation. The aim of this study was to elucidate the methylation status of HMGCR gene and evaluate its impact on cardiovascular morbidity and mortality in patients receiving hemodialysis. Method We analyzed DNA in plasma of 21 hemodialyzed patients before and after dialysis. Then bisulfite conversion was carried out to distinguish methylated and unmethylated form of DNA. The primers of HMGCR genes promoters were designed, after that methylation specific PCR and sequential analysis of PCR products were performed. Results Although the methylation rate of HMGCR gene dropped 9 patients during the hemodialysis session, no statistical significance of this demethylation was confirmed. No correlation of methylation status of HMGCR gene and cholesterol or phosphorus was confirmed. Hypomethylated promoter of HMGCR gene was found in 6 patients, who either underwent amputation of lower extremity due to arterial ischemia or has deceased due to cardiovascular event during next 6 month of follow-up period. Conclusion This study suggests that both DNA demethylation and consecutive increased expression of HMGCR gene could be predictors of high risk of cardiovascular morbidity and mortality in hemodialyzed diabetic patients.

Abstract PO4-20-04: A Randomized Window of Opportunity Study of Preoperative Letrozole and Simvastatin Versus Letrozole Alone in Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer

Abstract Hormone receptor positive (HR+), HER2 negative (HER2-) breast cancers are poor responders to immunotherapy. There is a need for innovative approaches to improve immune responses in these tumors. The combination of statins and aromatase inhibitors have demonstrated antiproliferative and immunomodulatory properties. However, this combination has never been studied in the preoperative setting; thus, our ongoing study represents an opportunity to investigate this approach. We designed a randomized two-arm presurgical “window of opportunity” trial to evaluate the effects of letrozole and simvastatin versus letrozole alone 14 days prior to surgery. Tissue and blood will be obtained at baseline and 14 days after completion of therapy at the time of surgery. Inflammatory markers in the blood and multiplex immunohistochemistry (IHC) in tissue will be assessed. To be eligible for the trial, participants must be postmenopausal women with histologically confirmed stage I-III HR+, HER2- invasive breast cancer with baseline ki-67 ≥10% that have not received prior chemotherapy, endocrine therapy, and/or immunotherapy within 3 months prior to trial enrollment. They should also not have received any cholesterol lowering medication within 3 months prior to trial enrollment. The primary objective is to determine if the addition of simvastatin to letrozole compared to letrozole alone will result in a decrease in geometric mean % change in ki-67 from pre-surgical baseline to 14 days following preoperative therapy. Ki-67 is a validated surrogate marker for disease-free survival in HR+, HER2- breast cancer. The main secondary objective is to determine if the addition of simvastatin to letrozole compared to letrozole alone will result in increased immune activation from pre- to post-treatment based on the evaluation of the immune subtype composition in tissue via multiplex immunofluorescence. We aim to enroll 16 patients in each arm to achieve 90% power and detect a minimum difference of 7.5% in ki-67 using a two-sided Mann-Whitney U or Wilcoxon Rank-Sum test. After accounting for a possible drop off rate of 20%, the study’s target accrual will be 40 participants. Statistical analyses will be performed using SAS 9.4. the significance level will be set at alpha = 0.1. Descriptive statistics will be applied to tissue and blood biomarkers of interest at 2 designated time points, prior to preoperative therapy and following completion of preoperative therapy. The absolute change or percentage change of those biomarkers will also be calculated and compared between the 2 arms using the nonparametric Mann-Whitney U test. The correlation among biomarkers will be described by Pearson correlation coefficient with 95% confidence interval. The p-value will be adjusted by Benjamini-Hochberg procedure to control the false discovery rate. All adverse events experienced data will be described by summary statistics and will be assessed according to CTCAE version 5.0. Currently, the study has accrued 2 participants. After completing accrual, we will assess whether the tumor-immune milieu has undergone modulation, resulting in a more immunogenic environment. If an immunogenic effect is demonstrated, this will provide rationale for a future multi-center trial assessing the combination of letrozole, simvastatin, and immunotherapy. Citation Format: Ruth Sacks, Elizabeth Haas, Jade Jones, Manali Bhave, Keerthi Gogineni, Jane Meisel, Demetria Smith-Graziani, Suchi Pakkala, Sarah Friend, Cletus Arciero, Lauren Postlewait, Clara Farley, Cathy Graham, Toncred Styblo, Monica Rizzo, Rhonda Pickett, Nicholas Crasta, Lori Brown, Xiaoxian Li, Sunil Badve, Madhav Dhodapkar, Kevin Kalinsky. A Randomized Window of Opportunity Study of Preoperative Letrozole and Simvastatin Versus Letrozole Alone in Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-04.

Measuring the Influence of Side Effect Expectations, Beliefs, and Incident Side Effects on the Risk for Drug Discontinuation Among Individuals Starting New Medications, a Cross-sectional Study.

To measure the impact of beliefs, expectations, side effects, and their combined effects on the risk for medication nonpersistence. Using a cross-sectional design, individuals from Saskatchewan, Canada who started a new antihypertensive, cholesterol-lowering, or antihyperglycemic medication were surveyed about risk factors for nonpersistence including: (a) beliefs measured by a composite score of three questions asking about the threat of the condition, importance of the drug, and harm of the drug; (b) incident side effects attributed to treatment; and (c) expectations for side effects before starting treatment. Descriptive statistics and logistic regression models were used to quantify the influence of these risk factors on the outcome of nonpersistence. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Among 3,029 respondents, 5.8% (n=177) reported nonpersistence within four months after starting the new drug. After adjustment for numerous covariates representing sociodemographics, health-care providers, medication experiences and beliefs, both negative beliefs (OR: 7.26, 95%CI: 4.98-10.59) and incident side effects (OR: 8.00, 95%CI: 5.49-11.68) were associated with the highest odds of nonpersistence with no evidence of interaction. In contrast, expectations for side effects before starting treatment exhibited an important interaction with incident side effects following treatment initiation. Among respondents with incident side effects (n=741, 24.5%), the risk for early nonpersistence was 11.5% if they indicated an expectation for side effects before starting the medication compared to 23.6% if they did not (adjusted OR: 0.38, 95%CI: 0.25-0.60). Expectations for side effects may be a previously unrecognized but important marker of the probability to persist with treatment. A high percentage of new medication users appeared unprepared for the possibility of side effects from their new medication making them less resilient if side effects occur.

Cardiovascular Disease Burden in Persons with Mental Illness: Comparison between a U.S. Psychiatry Outpatient Sample and a U.S. General Population Sample

Background. Cardiovascular disease (CVD) and depression are the leading causes of disability in the U.S. Using electronic health record data, we describe the CVD burden among persons with mental illness enrolled in the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) Registry between 2015 and 2020. Methods. CVD burden assessment included prevalence of CVD conditions (any major CVD or individual CVD risk factors), indicated medication prescriptions for CVD risk factors, and mean levels of body mass index (BMI, kg/m2), glycosylated hemoglobin (HbA1C, %), glucose (mg/dl), and lipids (mg/dl). We compared the CVD burden between the PCARES sample to a representative sample of adults from the U.S. general population (NHANES 2013-2016) using one-sample chi-square/t-tests for proportions/means. The CVD burden in NHANES participants was adjusted to PCARES age, race, and sex statistics. Results. The PCARES sample (N=3556) had a mean (SE) age of 42.4 (0.3) years and comprised 63.0% women, 85.0% non-Hispanic Caucasians, and 41.0% with major depressive disorder. CVD burden was higher in the PCARES sample compared to NHANES participants for any major CVD (8.6% vs. 4.6%), diabetes (18.4% vs. 10.4%), BMI (30.3 vs. 28.3), HbA1C (6.1 vs. 5.6), cholesterol (185.6 vs. 181.7), triglycerides (153.3 vs. 136.1), and indicated antihypertensive (94.3% vs. 76.9%) and cholesterol-lowering (49.5% vs. 36.7%) medications (Bonferroni-corrected p=0.03 for each outcome). The CVD burden was lower in the PCARES sample compared to NHANES participants for hypertension (45.9% vs. 50.4%), dyslipidemia (43.2% vs. 61.9%), HDL-C (48.4 vs. 41.4), and LDL-C (107.9 vs. 112.0) (Bonferroni-corrected p=0.03 for each outcome). Glucose levels (110.9 vs. 111.9) and indicated antidiabetic medications (87.4% vs. 86.6%) were similar in the two samples (p>0.05). Conclusions. The CVD burden was higher in persons with mental illness compared to the U.S. general population. Integrated mental and physical healthcare services could reduce long-term disability among persons with mental illness.

Abstract 4429: Plasma metabolic profiles in association with subsequent risk of colorectal cancer in the UK Biobank cohort

Abstract Background: Dysregulation of metabolic processes contributes to colorectal cancer (CRC) etiology. We aimed to comprehensively evaluate the prospective associations between pre-diagnostic metabolic biomarkers and CRC risk in 230,420 UK Biobank participants. Methods: A total of 249 metabolic biomarkers were measured by nuclear magnetic resonance spectroscopy from baseline plasma samples. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of metabolic biomarkers with CRC risk after adjusting for potential confounders. Subgroup analyses were performed by sex and CRC subsites (i.e., proximal colon, distal colon, rectum). We also conducted factor analyses to identify latent factors and examined their associations with CRC risk. Results: During a median follow-up time of 9.7 years, 2,410 incident primary CRC cases were identified after excluding participants diagnosed with CRC within two years after blood collection. After correcting for multiple testing, 50 metabolic biomarkers, including lipids and lipoproteins, fatty acids, ketone bodies, and inflammation, were significantly associated with incident CRC risk. No statistically significant differences were observed for the biomarker-CRC associations by sex and CRC subsite. In the sensitivity analysis, excluding cholesterol-lowering medication users did not alter the main findings. In factor analyses, we identified a significant association of CRC risk (HR = 1.08; 95% CI = 1.04-1.13; P-value = 6.89×10-5) with a metabolite pattern which was positively correlated with triglycerides and inversely correlated with relative concentrations of omega-6 fatty acids and polyunsaturated fatty acids. Conclusion: We identified multiple metabolic biomarkers and a metabolite pattern associated with CRC risk in a large prospective cohort. These findings suggest lipid metabolism may contribute to carcinogenesis of the colorectum. Citation Format: Fangcheng Yuan, Guochong Jia, Wanqing Wen, Wei Zheng. Plasma metabolic profiles in association with subsequent risk of colorectal cancer in the UK Biobank cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4429.

Abstract P540: Sleep Duration, Rapid Eye Movement Sleep, and Subclinical Myocardial Damage

Introduction: Sleep is strongly linked to clinical cardiovascular disease and was added in 2022 to the AHA’s Life’s Essential 8. Optimizing sleep duration and quality may reduce the risk of cardiovascular disease. Few studies have examined self-reported sleep duration and percent time in rapid eye movement (REM) sleep measured by single night in-home polysomnography with high sensitivity cardiac troponin T (hs-troponin T), a biomarker of subclinical cardiovascular disease. Methods: We conducted a cross-sectional study of adults without a history of cardiovascular disease who participated in both the Atherosclerosis Risk in Communities (ARIC) Study and the Sleep Heart Health Study (SHHS) in 1995-1998. We used linear regression with sleep duration and percentage time of REM sleep modeled as predictors with restricted cubic splines and examined associations with the outcome, hs-troponin T. We adjusted for age, sex, body mass index, waist-to-hip ratio, alcohol intake, smoking status, systolic blood pressure, hypertension medication use, diabetes, HDL- and LDL-cholesterol, and cholesterol-lowering medication use. Results: Among 1,587 participants (mean age 63, 54% female), the mean sleep duration was 7.3 hours, and mean % REM time was 20.7. Sleep duration was not associated with hs-troponin T ( Figure, Panel A ). However, percentage REM sleep was negatively associated with hs-troponin T, but with a threshold effect; there was a negative linear association of hs-troponin T with % REM sleep but only at values <15% ( Figure, Panel B ). Conclusion: While self-reported sleep duration was not associated with TnT levels, there was evidence that low % REM sleep, a specific neurophysiological sleep state, was associated with subclinical cardiovascular disease. These findings suggest that multiple sleep dimensions should be considered in efforts to optimize cardiovascular health.

Discovery and Exploration of Lipid-Modifying Drug Targets for ALS by Mendelian Randomization.

Observational studies have faced challenges in identifying replicable causes for amyotrophic lateral sclerosis (ALS). To address this, we employed an unbiased and data-driven approach to discover and explore potential causal exposures using two-sample Mendelian randomization (MR) analyses. In the phenotype discovery stage, we assessed 3948 environmental exposures from the UK Biobank and utilized ALS summary statistics (Europeans, 20,806 cases, 59,804 controls) as the outcome within a phenome-wide MR pipeline. Through a range of sensitivity analyses, two medication traits were identified to be protective for ALS. In the target exploration stage, we further conducted drug target MR analyses using the latest and trans-ethnic summary data on lipid-related traits and ALS (Europeans, 27,205 cases, 110,881 controls; East Asians, 1234 cases, 2850 controls). Our aim was to explore potential causal drug targets through six lipid-modifying effects. These comprehensive analyses revealed significant findings. Specifically, "cholesterol-lowering medication" and "atorvastatin" survived predefined criteria in the phenotype discovery stage and exhibited a protective effect on ALS. Further in the target exploration stage, we demonstrated that the therapeutic effect of APOB through LDL-lowering was associated with reduced ALS liability in Europeans (OR = 0.835, P = 5.61E - 5). Additionally, the therapeutic effect of APOA1 and LDLR through TC-lowering was associated with reduced ALS liability in East Asians (APOA1, OR = 0.859, P = 5.38E - 4; LDLR, OR = 0.910, P = 2.73E - 5). Overall, we propose potential protective effects of cholesterol-lowering drugs or statins on ALS risk from thousands of exposures. Our research also suggests APOB, APOA1, and LDLR as noveltherapeutic targets for ALS and supports their potential protective mechanisms may be mediated by LDL-lowering or TC-lowering effects.

Identification of patients at risk of cardiovascular disease in greater Manchester in the VICTORION-Spirit study

Background: Inclisiran is a cholesterol-lowering small interfering RNA treatment licensed in the UK for lowering low-density lipoprotein cholesterol (LDL-C). VICTORION-Spirit (NCT04807400) is an implementation science study designed to provide evidence for inclisiran implementation within the National Health Service. The aim was to describe the process of patient identification employed in VICTORION-Spirit. Methods: A Phase IIIb, multicentre, randomised controlled study, VICTORION-Spirit is evaluating inclisiran implementation in participants with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents and elevated LDL-C. Feasibility Assessment and Recruitment System for Improving Trial Efficiency (FARSITE) software utilising natural language search functions identified patients who may benefit from inclisiran. FARSITE searches were performed within Salford, Manchester, Trafford and Bury Clinical Commissioning Groups to identify individuals with elevated LDL-C or total cholesterol and pre-existing cardiovascular disease (CVD) or at risk of ASCVD. Results: FARSITE used ‘total cholesterol >4 mmol/l’ terminology rather than ‘LDL-C’; the former yielded >3 times the number of eligible patients. The search for individuals with pre-existing CVD identified 24,196 people in a population of 560,969 (4.3%); including ‘total cholesterol >4 mmol/l’ identified 10,431 individuals with pre-existing CVD and elevated total cholesterol. Searches for individuals at risk of ASCVD identified 65,457 people, narrowing to 26,580 at risk of ASCVD plus elevated total cholesterol. The most discriminatory SNOMED concept codes and their prevalence within the dataset can inform national approaches to develop similar searches. Conclusions: FARSITE searches employed in VICTORION-Spirit identified a population at risk of ASCVD in Greater Manchester, England, who may benefit from a cholesterol-lowering medication such as inclisiran.

Association between chronic viral infection-related hospitalization and risk of cardiovascular disease: Apopulation-based cohort study.

Chronic viral infection induces immunosenescence and systemic low-grade inflammation, leading to worsened long-term outcomes. We sought to explore the short- and long-term effects of chronic viral infection on cardiovascular disease (CVD). Based on UK Biobank data, exposed group was identified as individuals who had chronic virus infection-related hospitalization (IRH). Unexposed group was randomly selected, matched by 5-year age interval, sex, and Charlson comorbidity index at a ratio up to 1:10. Restricted cubic splines were used to model time-varying effects of IRH in nonproportional Cox models. A cut-off value of 5 years was recorded and used in piecewise Cox proportional hazards models as we estimated short- and long-term effects of IRH on CVD. A total of 2826 exposed participants and 28 212 matched unexposed participants were included. Chronic viral IRH was associated with increased risk of CVD (0-5 years: hazard ratio, 1.57 [95% confidence interval: 1.32, 1.87] and 5+ years: 1.31 [1.06, 1.61]). Elevated risk of stroke was only observed within the initial 5-year follow-up (0-5 years: 1.91 [1.30, 2.81]). The short- and long-term associations were observed in herpes or hepatitis virus IRH with risk of CVD (all p < 0.05). Subgroup analysis revealed long-term association between chronic viral IRH and CVD among female (5+ years: 1.68 [1.27, 2.22]) but not among male. The association between chronic viral infection and elevated CVD risk appeared to be stronger among individuals who did not take cholesterol-lowering medication, antithrombotic medication, or certain antihypertensive medications (all p for interaction < 0.05). The risk of CVD event remained persistently higher within and over 5 years following chronic viral IRH, especially in individuals infected with herpes and hepatitis virus.

Genetically Linked Cognitive Dysfunction Induced by Cholesterol-Lowering Medications: A Two-Case Report

Genetically Linked Cognitive Dysfunction Induced by Cholesterol-Lowering Medications: A Two-Case Report

EGG CONSUMPTION: TRENDS OVER TIME, PATTERNS ACROSS THE LIFESPAN, AND PREDICTORS OF INTAKE

Abstract Eggs are an excellent nutritional source. However, the historical association of dietary cholesterol with serum cholesterol and thus, cardiovascular disease, along with restrictive dietary guidelines may have served as a barrier to egg consumption. This study examines trends over time, and predictors and patterns of egg consumption in older individuals followed for over 45 years. Participants were 6326 men and women enrolled in the Rancho Bernardo Study in 1972-74 when they were asked about the number of eggs consumed/week. Subsequent egg intake information was collected with food frequency questionnaires from subsamples attending clinic visits in 1988-91 (N=1627) and 1992-96 (N=1385), and with the original question on a 2021 mailed survey (N=710). Mean(□SD) eggs consumed was 3.6□3.0 in 1972-74, 1.8□2.1 in 1988-91, 1.8□2.2 in 1992-96, and 3.4□3.5 in 2021. Comparisons within 5-year categories of baseline age (&amp;lt; 20, 20-24, 25-29, 30-34, 35-39, &amp;gt;40) showed no differences in egg intake between 1972-74 and when older in 2021. Men consumed more eggs than women at all timepoints (p’s&amp;lt; 0.0001). Those with higher education (p&amp;lt; 0.0001) and diabetes (p=0.0009) consumed more eggs; those with high cholesterol or taking cholesterol lowering medication consumed fewer eggs in 1972-74 (p’s&amp;lt; 0.0001), but there were no differences by these factors by 2021. Egg consumption appears responsive to dietary guidelines, decreasing over time then increasing by 2021 to levels similar to the early 1970s. Among those young and middle-aged at baseline, egg intake patterns were similar 45 years later, when older. Cholesterol and cholesterol-lowering medication use are no longer factors in egg intake.

Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films.

Rosuvastatin (RSV) is a widely used cholesterol-lowering medication, but its limited bioavailability due to its susceptibility to stomach pH and extensive first-pass metabolism poses a significant challenge. A fast-dissolving film (FDF) formulation of RSV was developed, characterized, and compared to the conventional marketed tablet to address this issue. The formulation process involved optimizing the thickness, disintegration time, and folding durability. All formulations were assessed for in vitro disintegration, thickness, folding endurance, in vitro dissolution, weight, and content uniformity. The study's results revealed that the optimized RSV-FDF displayed a significantly faster time to maximum plasma concentration (tmax) of 2 h, compared to 4 h for the marketed tablet. The maximum plasma concentration (Cmax) for the RSV-FDF (1.540 µg/mL ± 0.044) was notably higher than that of the marketed tablet (0.940 µg/mL ± 0.017). Additionally, the pharmacodynamic assessment in male Wistar rats demonstrated that the optimized RSV-FDF exhibited an improved lipid profile, including reduced levels of low-density lipoproteins (LDLs), elevated high-density lipoproteins (HDLs), decreased triglycerides (TGs), and lower very-low-density lipoproteins (VLDLs) compared to the conventional tablet. These findings underscore the potential of RSV-FDFs as a promising alternative to enhance the bioavailability and therapeutic efficacy of rosuvastatin in treating dyslipidemia. The faster onset of action and improved lipid-lowering effects make RSV-FDFs an attractive option for patients requiring efficient cholesterol management.

Potential impact of high-density lipoprotein cholesterol in the postoperative outcomes of chronic subdural hematoma patients: multi-institutional study in Korea

BackgroundChronic subdural hematoma (CSDH) is a common clinical situation in neurosurgical practice, but the optimal treatment option is controversial. This study aimed to evaluate the effect of cholesterol-lowering medications on and how they affected the prognoses of CSDH patients.MethodsIn this multi-institutional observational study performed in Korea, data from recently treated CSDH patients were gathered from 5 hospitals. A total of 462 patients were collected from March 2010 to June 2021. Patient clinical characteristics, history of underlying diseases and their treatments, radiologic features, and surgical outcomes were analyzed.ResultsSeventy-five patients experienced recurrences, and 62 had reoperations after the initial burr hole surgery. Among these, 15 patients with recurrences and 12 with reoperations were taking cholesterol-lowering medications. However, the use of medications did not significantly affect recurrence or reoperation rates (P = 0.350, P = 0.336, respectively). When analyzed by type of medication, no clinically relevant differences in total cholesterol (TC), triglyceride (TG), or low-density lipoprotein cholesterol (LDL-C) levels were identified. The combination of a statin drug and ezetimibe significantly elevated high-density lipoprotein cholesterol (HDL-C) levels (P = 0.004). TC, LDL-C, and TG levels did not significantly affect patient prognoses. However, HDL-C levels and recurrence (odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.94–0.99; p = 0.010) were negatively correlated. An HDL-C level of 42.50 mg/dL was identified as the threshold for recurrence and reoperation.ConclusionsIn this study, using cholesterol-lowering medications did not significantly impact the prognosis of patients who underwent surgical management for a chronic subdural hematoma. However, the findings showed that the higher the HDL-C level, the lower the probability of recurrence and reoperation.

Successful ESC recommended LDL-C reduction after percutaneous coronary intervention: real-world data from the contemporary ZON-HR registry

Abstract Background Low density lipoprotein-cholesterol (LDL-C) reduction in patients who underwent percutaneous coronary intervention (PCI) is recommended by ESC guidelines to prevent secondary events. Lipid lowering treatment is indicated to reach a LDL-C of less than 1.4mmol/l in these very high risk patients. The ‘’Zuid-Oost Nederland Heart Registry’’ (ZON-HR) is a multicentre prospective registry designed to improve secondary prevention after PCI by a patient-tailored approach. Purpose Cholesterol management in patients after percutaneous coronary intervention (PCI) from the ZON-HR was evaluated. Methods Since November 2020 real-world data from 4628 patients who underwent PCI were collected in four hospitals. Patient characteristics, LDL-C values at baseline and after 30 days and medication at discharge were collected. The association between predefined variables and a LDL-C &amp;lt;1.4 mmol/l was assessed in multivariable logistic regression. Results LDL-C at baseline and one-month follow-up was complete in 306 patients. This number is limited, because LDL-C was not routinely tested in every patient at baseline and during 30 day follow-up. Patients with a chronic coronary syndrome (CCS) undergoing PCI were significantly older compared to patients with ACS (66.8 vs 63.9 years)(table 1). After one month, the LDL-C value decreased significantly both in ACS as well as CCS patients. No significant differences in cholesterol lowering medication at discharge between CCS and ACS patients were observed. Statins (87.8%) were most frequent prescribed, with low numbers of new therapies (8.2% ezetimibe, 2.6% PCSK-9 inhibitor). The goal LDL &amp;lt;1.4 mmol/l was reached in 33% of patients. Lower LDL-C levels at baseline, ACS indication for PCI, and a combination of lipid lowering treatment were independent predictors for achieving the goal LDL-C &amp;lt;1.4 (table 2). Conclusion Our contemporary registry reveals the following important observations: 1) LDL-C assessment at one month follow-up is performed in a minority of patients. 2) The LDL-C goal of 1.4 mmol/l is reached in a minority of patients. 3) Predictors for reaching the ESC recommended target include an ACS indication and combination lipid lowering treatment, emphasizing the importance of secondary prevention.Baseline characteristicsPredictors reaching LDL-C target value

Evaluation of Short-Term Toxicity and Cholesterol-Lowering Effects in Rats Exposed to Dietary Fiber Derived from Cassava Pulp.

The dietary fiber extracted from cassava pulp, composed of crude fiber, neutral detergent fiber (NDF), and cellulose content, demonstrates promise as a functional food ingredient. The study's objectives encompassed the assessment of short-term toxicity and the evaluation of its potential cholesterol-lowering effects. The results indicated that cassava pulp dietary fiber (CDF) is well-tolerated with non-toxic thresholds determined at 10.01 g/kg body weight/day for male rats and 11.21 g/kg body weight/day for female rats during the short-term toxicity assessment. Furthermore, CDF exhibited notable cholesterol-lowering effects, significantly reducing serum triglyceride and serum total cholesterol levels, along with decreased liver total lipids and liver cholesterol levels. In contrast, it led to significant increases in fecal total lipids and cholesterol when compared to the control group. Most notably, there were no significant differences in terms of serum triglyceride, serum total cholesterol, liver total lipids, and liver cholesterol between CDF and the conventional cholesterol-lowering medication, simvastatin. These findings underscore the potential of cassava pulp dietary fiber as a natural and safe alternative for managing hyperlipidemia and related conditions. It offers a valuable avenue for the development of functional foods aimed at improving cardiovascular health and further investigation for its potential application in the field of nutraceuticals.

Abstract 11950: Cardiometabolic Health Disparities in Sexual Minority Men

Aim: We summarize 3 meta-analyses conducted on hypertension, dyslipidemias, and obesity, comparing sexual minority men (SMM) and heterosexual men. Methods: We conducted a systematic search in 4 databases to identify studies comparing SMM and heterosexual men in measures for the three relevant outcomes. Prevalence rates, continuous, and inverse variance estimates were generated through random effect models and reported through proportions, mean differences (MDs), and odds ratios (ORs), respectively, with their corresponding 95% confidence intervals [in brackets]. Results: Hypertension. 20 studies showed men who have sex with men (MSM) were less likely (OR 0.34 [0.16, 0.70]) whereas bisexual men were more likely (OR 2.25 [1.54, 3.28]) to report hypertension. Bisexual men are more likely to use antihypertensive medication (OR 1.44 [CI 1.11, 1.85]) and all SMM had higher diastolic blood pressure (DBP; MD 1.46 [1.38, 1.55] mmHg). Dyslipidemias. 10 eligible studies showed lower prevalence of elevated cholesterol for SMM (45.21%; χ 2 [1]=54.78; P &lt;0.001) that does not hold with inverse variance analyses (OR 1.04 [0.91, 1.18]). While bisexual men—but not MSM—are more likely to take cholesterol-lowering medication (OR 1.47 [1.11, 1.93]) and present with lower cholesterol levels (MD –6.80 [–7.27, –6.34] mg/dL), MSM—but not bisexual men—present with lower triglyceride levels (MD –25.67 [–39.80, –11.55] mg/dL). Obesity. 43 studies identified lower prevalence of overweight, obesity, and elevated BMI among SMM, consistent with lower body mass index (BMI; MD –1.50 [–1.93, –1.08] kg/m 2 ) and decreased likelihood of overweight (OR 0.75 [0.64, 0.88]) and obesity (OR 0.84 [0.78, 0.90]). Conclusions: SMM present more frequently with a history of hypertension, linked to elevated DBP—a marker of hypertension at earlier ages. Bisexual men are prescribed cholesterol-lowering medication and present with lower cholesterol levels; MSM present with lower triglyceride levels. Lower rates/likelihood of overweight, obesity, and elevated BMI may point to the obesity paradox—a sustained catabolic state presenting with lower BMI but poor cardiovascular outcomes—which, in connection to other stressors, warrants further research on cardiovascular disparities.

Impact of Dyslipidemia Medications on the Prevalence of Diabetic Retinopathy Among a Large US Cohort

Background and Objective: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. Patients and Methods: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022. Prevalence and prevalence odds ratios (POR) were calculated. Results: Patients taking pitavastatin (OR 0.64, 95% CI 0.49, 0.84), fenofibrate (OR 0.83, CI 0.79, 0.87), or evolocumab (OR 0.80, CI 0.68, 0.95) had lower POR of proliferative DR compared to nonproliferative DR. Patients taking any cholesterol medication had a lower POR of vitreous hemorrhage. Patients taking fibrates also had lower POR of neovascular glaucoma. Conclusion: This exploratory study highlights positive associations between DR and dyslipidemia and medications that may have fewer worsening events in DR patients. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:626–633.]

Preventive Cardiovascular Care for Hypercholesterolemia in US Emergency Departments: A National Missed Opportunity.

Hypercholesterolemia (HCL) affects nearly half of Emergency Department (ED) patients who present with possible acute coronary syndrome (ACS). However, it is unknown whether US ED providers obtain lipid panels, calculate 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and prescribe cholesterol-lowering medications for these patients. We conducted a nationwide cross-sectional ED survey from April 18, 2023, to May 12, 2023. An electronic survey assessing current preventive HCL care practices for patients being evaluated for ACS. A convenience sample was obtained by sharing the survey with ED medical directors, chairs, and senior leaders using emergency medicine professional organization listservs and snowball sampling. Responding EDs were categorized as being associated with an academic medical center (AMC) or not (non-AMC). During the 4-week study period, 110 EDs (50 AMC and 60 non-AMC EDs) across 39 states responded. Just 1.8% (2/110) stated that their providers obtain a lipid panel on at least half of patients with possible ACS and only one ED (0.9%) responded that its providers calculate 10-year ASCVD risk and prescribe cholesterol medication for the majority of eligible patients. Most reported never obtaining lipid panels (60.9%, 67/110), calculating 10-year ASCVD risk (55.5%, 61/110), or prescribing cholesterol-lowering medications (52.7%, 58/110). The vast majority of US ED providers do not provide preventive cardiovascular care for patients presenting with possible ACS. Most ED providers do not evaluate for HCL, calculate ASCVD risk, or prescribe cholesterol-lowering medications for these patients.

Development and application of pharmacological statin-associated muscle symptoms phenotyping algorithms using structured and unstructured electronic health records data.

Statins are widely prescribed cholesterol-lowering medications in the United States, but their clinical benefits can be diminished by statin-associated muscle symptoms (SAMS), leading to discontinuation. In this study, we aimed to develop and validate a pharmacological SAMS clinical phenotyping algorithm using electronic health records (EHRs) data from Minnesota Fairview. We retrieved structured and unstructured EHR data of statin users and manually ascertained a gold standard set of SAMS cases and controls using the published SAMS-Clinical Index tool from clinical notes in 200 patients. We developed machine learning algorithms and rule-based algorithms that incorporated various criteria, including ICD codes, statin allergy, creatine kinase elevation, and keyword mentions in clinical notes. We applied the best-performing algorithm to the statin cohort to identify SAMS. We identified 16 889 patients who started statins in the Fairview EHR system from 2010 to 2020. The combined rule-based (CRB) algorithm, which utilized both clinical notes and structured data criteria, achieved similar performance compared to machine learning algorithms with a precision of 0.85, recall of 0.71, and F1 score of 0.77 against the gold standard set. Applying the CRB algorithm to the statin cohort, we identified the pharmacological SAMS prevalence to be 1.9% and selective risk factors which included female gender, coronary artery disease, hypothyroidism, and use of immunosuppressants or fibrates. Our study developed and validated a simple pharmacological SAMS phenotyping algorithm that can be used to create SAMS case/control cohort to enable further analysis which can lead to the development of a SAMS risk prediction model.

Does altitude have an effect on stroke mortality and hospitalization risk? A comprehensive evaluation of United States data

BackgroundGlobally, stroke is a leading cause of death among people over 50 years of age. In the United States alone, over 150,000 people die due to stroke every year. Environmental factors such as altitude may play a role in these outcomes; however, their effects have not yet been comprehensively explored. The objective of this study is to evaluate the effect of altitude along with other covariates on stroke mortality and hospitalization rates in adults.MethodsThis study utilized altitude, stroke mortality and hospitalization rates; antihypertensive and cholesterol-lowering medication usage; smoking prevalence; and sociodemographic data (MH-SVI) obtained from government databases for 3,141 counties in the United States from 2018 to 2020. Data were analyzed using generalized additive models with and without adjustments for covariates.ResultsUnadjusted models show that altitude has a comparable significant negative effect on mortality rates for Black and white populations. When including all covariates, altitude continues to have a significant protective effect against stroke fatalities in white populations (retaining 26.6 and 53.8% of the effect magnitude for cardiovascular disease (CVD) and stroke mortality, respectively), a non-significant effect in the Black population, and a detrimental effect in Hispanic and Asian Pacific populations for CVD mortality (a 21.6 and 39.1% effect increase, respectively).ConclusionOur findings add to the growing body of evidence that environmental factors add to disparities between racial groups and play a significant role in CVD and stroke mortality. The effect of altitude is comparable in size to that of smoking, medication usage, and social determinants of health.