Baseline Low-density Lipoprotein Cholesterol Research Articles

Risk of Cardiovascular Disease according to Baseline Low-Density Lipoprotein Cholesterol Level in Different Age Groups in Korean Diabetes Population: A Cohort Study.

The association between low-density lipoprotein (LDL-C) levels and cardiovascular disease (CVD) risk in different age groups within the diabetes mellitus (DM) population remains unclear. The cohort study was conducted to investigate this relationship. We assessed the 2009 to 2012 Korean National Health Screening and National Health Insurance Service records, with follow-up to the primary outcome (myocardial infarction [MI] or stroke) or December 2018. After excluding the participants with a history of MI or stroke, 2,227,394 participants with DM were included and categorized according to baseline LDL-C levels and age. Cox proportional hazards modeling was conducted. The CVD risk of age <40 years and LDL-C <70 mg/dL was set as the reference. In each age group, LDL-C <70 mg/dL was used as a reference for the subgroup analysis. The cut-off LDL-C value for increased MI risk in each age group varied (<40 years old, LDL-C ≥160 mg/dL: hazard ratios [HR], 2.03; 95% confidence interval [CI], 1.644 to 2.506) (40-49-year-old, LDL-C <115 mg/dL: HR, 1.245; 95% CI, 1.04 to 1.489) (50-59-year-old, LDL-C <115 mg/dL: HR, 1.21; 95% CI, 1.014 to 1.445) (60-69-year-old, LDL-C <145 mg/dL: HR, 1.229; 95% CI, 1.022 to 1.479) (≥70 years old group, LDL-C <100 mg/dL: HR, 1.238; 95% CI, 1.018 to 1.504). The cut-off LDL-C values for increased stroke risk varied in each age subgroup (<40 years old, LDL-C ≥160 mg/dL: HR, 1.395; 95% CI, 1.094 to 1.779) (40-49-year-old, LDL-C <145 mg/dL: HR, 1.13; 95% CI, 1.019 to 1.253) (50-59-year-old, LDL-C <160 mg/dL: HR, 1.079; 95% CI, 1.008 to 1.154) (60-69-year-old, LDL-C <130 mg/dL: HR, 1.07; 95% CI, 1.022 to 1.119) (≥70 years old, LDL-C <115 mg/dL: HR, 1.064; 95% CI, 1.019 to 1.112). The effect of LDL-C on the risk of CVD differs depending on the age of the population with DM.

Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study.

The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was -7.1% (-10.7%, -3.6%) and -3.9% (-5.1%, -2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

Statin treatment in stroke patient with low‐density lipoprotein cholesterol levels below 70 mg/dL

Background and purposeThe effectiveness of hyperlipidemia treatment in strokes secondary prevention has been established. However, whether pretreatment with statins could confer protective effects when a patient's baseline low-density lipoprotein cholesterol (LDL-C) level is <70 mg/dL remains uncertain. Additionally, the ability of statin treatment to reduce poststroke complications, mortality, and recurrence in this patient group is unclear. Methods and resultsIn this retrospective observational study, we enrolled patients who had experienced an ischemic stroke with LDL-C levels <70 mg/dL. We analyzed the association of statin use with baseline characteristics, stroke severity, in-hospital complications, mortality rates, stroke recurrence rate, and mortality rate. Patients who used and patients who did not use statins were similar in terms of age and sex. Patients using statins had higher rates of diabetes mellitus, hypertension, prior stroke, and coronary artery disease but a lower incidence of atrial fibrillation. Stroke severity was less pronounced in those using statins. We also evaluated the relationship between in-hospital statin use and complications. We noted that in-hospital statin use was associated with lower rates of infection, hemorrhagic transformation, gastrointestinal hemorrhage, and mortality, as well as higher rates of positive functional outcomes. The 1-year recurrence rate was similar in both groups. ConclusionsStatin use is associated with milder strokes and improved poststroke outcomes, even in patients with well-controlled LDL levels. Neurologists may consider prescribing statins for patients with ischemic stroke who do not overt hyperlipidemia. Further research into potential underlying mechanisms is warranted.

Progression rate of radiation-induced carotid stenosis in head and neck cancer survivors after statin treatment: a retrospective cohort study.

Whether statin treatment is effective in retarding the progression of radiation-induced carotid stenosis (RICS) in head and neck cancer (HNC) survivors has not been well studied. The purpose of this study was to assess the association of statin treatment with RICS progression rate in HNC survivors after radiotherapy. We conducted a retrospective cohort study at Sun Yat-sen Memorial Hospital, Sun Yat-sen University in Guangzhou, China. Between January 2010 and December 2021, we screened HNC survivors whose carotid ultrasound scans had shown stenosis of the common and/or internal carotid arteries. The primary outcome was the RICS progression rate. We compared eligible patients treated with statins with those who did not in multivariable Cox regression models. A total of 200 patients were included in this study, of whom 108 received statin treatment and 92 did not. Over a mean follow-up time of 1.5 years, 56 (28.0%) patients showed RICS progression, 24 (42.9%) and 32 (57.1%) in the statin and control groups, respectively. The statin group showed less RICS progression than the control group (adjusted-HR 0.49, 95% CI 0.30-0.80, P = 0.005). In the subgroup analysis, there was no significant interaction in the effect of statins on lowering RICS progression rate in the subgroups stratified by baseline low-density lipoprotein cholesterol (LDL-C) levels (P for interaction = 0.53) or baseline degrees of stenosis (P for interaction = 0.50). Statin treatment was associated with a lower risk of RICS progression in patients with HNC after radiotherapy, regardless of baseline LDL-C level and baseline stenosis degrees.

Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular toxicity from androgen deprivation therapy in men with prostate cancer.

312 Background: Androgen deprivation therapy (ADT) with agonists of the gonadotropin releasing hormone (GnRH) receptor (e.g. leuprolide) is associated with coronary artery disease and major adverse cardiovascular (CV) events. CHIP, an age-related expanded somatic blood cell clone without other hematologic abnormalities, is associated with inflammation and accelerated atherosclerosis. Whether CHIP is associated with adverse CV outcomes in patients receiving ADT is unknown. Methods: Twenty-five men with localized prostate cancer pursuing radiotherapy plus ≥ 6 months of leuprolide were enrolled on a prospective biorepository. Using pre-treatment blood samples, whole exome sequencing libraries were generated; identified variants were filtered to retain &lt;1% MAF variants found amongst the three most common CHIP genes ( DNMT3A, TET2, ASXL1). Pre-treatment and 6-month blood samples from each patient subsequently were analyzed using a commercially available, validated 4-protein risk score that is predictive of 4-year major adverse CV events (Prevencio Inc HART CVE, Seattle WA). Multivariable logistic regression measured the association of CHIP with increased CV risk after initiation of leuprolide, defined as a clinically significant rise in 4-protein risk score at six months compared with baseline. Results: Median age was 70 years (IQR 65-76), 10 men (40%) were Black, and 4 men (16%) had a history of myocardial infarction. CHIP gene variants were found in 7 men (28%). Amongst the men with CHIP variants, 6 (85.7%) were Black. Amongst the entire cohort, 11/25 (44%) men had a clinically significant rise in CV risk score after six months of ADT. These men, compared with those who did not experience a rise in CV risk, were more often Black (72.7% versus 14.3%), on anti-hypertensive medication (72.7% versus 14.3%), and had higher baseline LDL cholesterol level (median 98 versus 81 mg/dL). On univariate analysis, harboring ≥1 CHIP variant was associated with a significantly increased odds of having an elevated CV risk score after 6 months of ADT. On multivariable analysis, after adjusting for race, anti-hypertensive medication use, and baseline LDL cholesterol, harboring ≥1 CHIP variant was associated with increased odds of having an elevated CV risk score after 6 months of ADT (adjusted OR 1.44, 95% CI 0.88-1.83), which did not meet statistical significance but limited by small sample size. Conclusions: Six months of GnRH-agonist leuprolide resulted in a rise in CV risk score in 44% of this cohort. CHIP variants, identified in 28% of this cohort, was associated with increased odds of experiencing a rise in CV risk score. Notably, Black men were more likely to harbor CHIP and experience increased CV risk after 6 months of leuprolide, respectively. Larger studies are underway to determine if CHIP variants may serve as a biomarker of ADT-induced CV risk, especially in older Black men.

Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol

Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified. To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults. A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023. LDL-C, cumulative past LDL-C, FH variant status. Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults. Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant. In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.

Oreo Cookie Treatment Lowers LDL Cholesterol More Than High-Intensity Statin therapy in a Lean Mass Hyper-Responder on a Ketogenic Diet: A Curious Crossover Experiment.

Recent research has identified a unique population of 'Lean Mass Hyper-Responders' (LMHR) who exhibit increases in LDL cholesterol (LDL-C) in response to carbohydrate-restricted diets to levels ≥ 200 mg/dL, in association with HDL cholesterol ≥ 80 mg/dL and triglycerides ≤ 70 mg/dL. This triad of markers occurs primarily in lean metabolically healthy subjects, with the magnitude of increase in LDL-C inversely associated with body mass index. The lipid energy model has been proposed as one explanation for LMHR phenotype and posits that there is increased export and subsequent turnover of VLDL to LDL particles to meet systemic energy needs in the setting of hepatic glycogen depletion and low body fat. This single subject crossover experiment aimed to test the hypothesis that adding carbohydrates, in the form of Oreo cookies, to an LMHR subject on a ketogenic diet would reduce LDL-C levels by a similar, or greater, magnitude than high-intensity statin therapy. The study was designed as follows: after a 2-week run-in period on a standardized ketogenic diet, study arm 1 consisted of supplementation with 12 regular Oreo cookies, providing 100 g/d of additional carbohydrates for 16 days. Throughout this arm, ketosis was monitored and maintained at levels similar to the subject's standard ketogenic diet using supplemental exogenous d-β-hydroxybutyrate supplementation four times daily. Following the discontinuation of Oreo supplementation, the subject maintained a stable ketogenic diet for 3 months and documented a return to baseline weight and hypercholesterolemic status. During study arm 2, the subject received rosuvastatin 20 mg daily for 6 weeks. Lipid panels were drawn water-only fasted and weekly throughout the study. Baseline LDL-C was 384 mg/dL and reduced to 111 mg/dL (71% reduction) after Oreo supplementation. Following the washout period, LDL-C returned to 421 mg/dL, and was reduced to a nadir of 284 mg/dL with 20 mg rosuvastatin therapy (32.5% reduction). In conclusion, in this case study experiment, short-term Oreo supplementation lowered LDL-C more than 6 weeks of high-intensity statin therapy in an LMHR subject on a ketogenic diet. This dramatic metabolic demonstration, consistent with the lipid energy model, should provoke further research and not be seen as health advice.

Impact of Bempedoic Acid on Total Cardiovascular Events

The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown. To determine the impact of bempedoic acid on the total incidence of MACE. Included in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022. Patients were randomly assigned to treatment with bempedoic acid or placebo daily. The primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups. A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients. Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.

Ten-year trends in lipid management among patients after myocardial infarction in South Korea.

Dyslipidemia is an important risk factor for acute myocardial infarction. However, real-world data on its prevalence and lipid management trends for Korean patients with acute myocardial infarction are limited. This study aimed to determine the 10-year temporal trends in dyslipidemia prevalence and lipid management in this patient population. The study used a merged database of two nationwide observational cohorts (2011-2020) that included 26,751 participants. The primary endpoints were the achievement rates of the (1) absolute low-density lipoprotein cholesterol (LDL-C) target of <70 mg/dL (<1.8 mmol/L), (2) relative LDL-C target reduction of >50% from the baseline, (3) absolute or relative LDL-C target (American target), and (4) both absolute and relative LDL-C targets (European target). The dyslipidemia prevalence increased from 11.1% to 17.1%, whereas the statin prescription rate increased from 92.9% to 97.0% from 2011 to 2020. The rate of high-intensity statin use increased from 12.80% in 2012 to 69.30% in 2020. The rate of ezetimibe use increased from 4.50% in 2016 to 22.50% in 2020. The high-intensity statin and ezetimibe prescription rates (0.20% to 9.30% from 2016 to 2020) increased gradually. The absolute and relative LDL-C target achievement rates increased from 41.4% and 20.8% in 2012 to 62.5% and 39.5% in 2019, respectively. The American (45.7% in 2012 to 68.6% in 2019) and European (16.5% in 2012 to 33.8% in 2019) target achievement rates also increased. The adoption of lipid management guidelines in clinical practice has improved. However, continued efforts are needed to reduce the risk of recurrent ischemic events.

Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction.

Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-c) from birth. About 85% of all FH cases are caused by pathogenic variants in the LDLR gene. Individuals with FH have increased cardiovascular risk, including a high risk of premature myocardial infarction (PMI). We conducted an opportunistic exome screening to identify variants in the LDLR gene among Vietnamese patients with PMI treated at a general hospital in southern Vietnam. A cascade testing for LDLR variants was conducted in their relatives within three generations, and the effects of the LDLR variant on the response to rosuvastatin treatment were also studied using a comparative before-and-after study design on those who were eligible. A total of 99 participants from the three generations of four PMI patients were recruited, mean age 37.3 ± 18.5 years, 56.6% males. Sanger sequencing revealed two variants in the LDLR gene: variant rs577934998 (c.664T>C), detected in 17 individuals within one family, and variant rs12710260 (c.1060+10G>C), found in 32 individuals (49.5%) in the other three families tested. Individuals harboring the variant c.664T>C had significantly higher baseline LDL-c and total cholesterol levels compared to those with variant c.1060+10G>C (classified as benign) or those without LDLR variants, and among the 47 patients subjected to a 3-month course of rosuvastatin therapy, those with variant c.664T>C had a significantly higher risk of not achieving the LDL-c target after the course of treatment compared to the c.1060+10G>C carriers. These findings provide evidence supporting the existence of pathogenic LDLR variants in Vietnamese patients with PMI and their relatives and may indicate the need for personalizing lipid-lowering therapies. Further studies are needed to delineate the extent and severity of the problem.

Achievement of target LDL-cholesterol level in patients with acute coronary syndrome undergoing percutaneous coronary intervention: The JET-LDL registry

BackgroundIn patients with acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level < 1.4 mmol/L (<55 mg/dL). MethodsThe JET-LDL is a multicenter, observational, prospective registry created to investigate levels of LDL-C in consecutive patients with ACS undergoing PCI at 35 Italian hospitals, and to report their lipid lowering therapies (LLT). Follow-up was planned at 1 and 3 months. LDL-C reduction >50% from baseline or level < 55 mg/dL at 1-month was the primary endpoint. ResultsA total of 1095 patients were included: median age was 67 (58–75); 33.7% were already on LLT. Baseline LDL-C levels was 105 (76.5–137) mg/dL. At hospital discharge all patients were on LLT: 98.1% received statins (as mono or combination therapy), ezetimibe and PCSK9i were used in 60.1% and 8.5% of cases, respectively. Primary endpoint was achieved in 62% (95% CI 58–65) of cases. At 1-month LDL-C levels dropped to 53 (38–70) mg/dL (p < 0.001 vs baseline) and it was <55 mg/dL in 53% (95% CI 49–57) of patients; however, PCSK9i were added to 7 further cases. At 3-months 58% (95% CI 55–62) of patients achieved the target level, but PCSK9i was added to only 11 new patients. ConclusionsIn this real-world registry of ACS patients undergoing PCI, recommend LDL-C levels were obtained in 62% of patients, but PCSK9i prescription was limited to 10% of cases. As LLT pattern appeared mainly improved at hospital discharge, an early and strong treatment should be considered.

Analysis of endothelial progenitor cell subtypes as clinical biomarkers for elderly patients with ischaemic stroke

Endothelial progenitor cells (EPCs), expressing markers for stemness (CD34), immaturity (CD133) and endothelial maturity (KDR), may determine the extent of post-stroke vascular repair. Given the prevalence of stroke in elderly, this study explored whether variations in plasmatic availability of certain EPC subtypes could predict the severity and outcome of disease in older patients. Blood samples were collected from eighty-one consented patients (≥ 65 years) at admission and days 7, 30 and 90 post-stroke. EPCs were counted with flow cytometry. Stroke severity and outcome were assessed using the National Institutes of Health Stroke Scale, Barthel Index and modified Rankin Scale. The levels of key elements known to affect EPC characteristics were measured by ELISA. Diminished total antioxidant capacity and CD34 + KDR + and CD133 + KDR + counts in early phases of stroke were associated with disease severity and worse functional outcome at day 90 post-stroke. Baseline levels of angiogenic agent PDGF-BB, but not VEGF, positively correlated with CD34 + KDR + numbers at day 90. Baseline LDL-cholesterol levels were inversely correlated with CD34 + KDR+, CD133 + KDR + and CD34 + CD133 + KDR + numbers at day 90. Close correlation between baseline CD34 + KDR + and CD133 + KDR + counts and the outcome of stroke proposes these particular EPC subtypes as potential prognostic markers for ischaemic stroke.

Caffeic Acid, Chlorogenic Acid, Garlic Acid, and Protocatechuic Acid as Hypolipidemic Agents

As the pathophysiology of dyslipidemias is clarified, one system is likely to emerge in which the underlying mechanism explains the phenotypic pattern observed on lipoprotein analysis. Every day, millions of vials of blood are drawn to assess patients’ risk for the disease. These tests measure three biomarkers, or factors in the blood known to be associated with CAD: low-density lipoproteins (LDL cholesterol), high-density lipoproteins (HDL cholesterol), and triglycerides. All three biomarkers are lipids – water-insoluble molecules that are among the structural and functional building blocks of living cells. Highly altered Body Mass Index (BMI) and hypertension are independent and reversible determinants for coronary artery disease. Hypolipidemia can prevent hyperlipidemic patients to be victim of coronary artery disease. This study was conducted to compare hypolipidemic effects of Niacin and Jujube fruit in primary as well as secondary hyperlipidemic patients. Study was conducted in 2023 at Jinnah Hospital Lahore, Pakistan. Sixty participants were enrolled of both gender male and female hyperlipidemic patients age range from 20 to 70 years. Written and explained consent was taken from all patients. They were divided in two groups. Group-I was advised to take two grams Niacin in divided doses for the period of two months. Group-II was advised to take 500 grams of fruit Jujube daily for the period of two months. Their baseline LDL and HDL cholesterol was determined by conventional method of measuring Lipid Profile. After two months therapy, their post treatment lipid profile was measured and mean values with ± SEM were analyzed biostatistically. Group-I which was on Niacin their LDL cholesterol decreased significantly and HDL cholesterol was increased significantly. In group-II patients LDL cholesterol was decreased significantly but HDL increase was not significant with p-value of &gt;0.05. It was concluded from the research work that Niacin is potent in lowering LDL and increasing HDL cholesterol, while Jujube has significant effect as LDL cholesterol lowering agent, but it does not increase HDL cholesterol significantly.

Clinical Significance of Serum High-Density Lipoprotein Cholesterol and Its Dynamic Change in Patients with Lymphoma-Associated Hemophagocytic Lymphohistiocytosis

Background: The lipid profile in serum is frequently dysregulated in lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). We aimed to explore the clinical significance of serum lipoprotein cholesterol in lymphoma-associated HLH. Methods: Patients with lymphoma-associated HLH were included. Serum levels of baseline low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) were collected. Serum levels of LDL-c and HDL-c after treatment (first test after treatment, time interval ≥ 14 days) were also collected. Results: A total of 169 lymphoma-associated HLH were included. T/NK-cell lymphomas (n=88, 52.1%) account for over half of cases. Low HDL-c (&amp;lt; 1.03 mmol/L) was observed in 161 (95.3%) patients and low LDL-c (&amp;lt; 2.6 mmol/L) was presented in 145 (85.8%) patients. The best cutoff of 0.50 mmol/L for HDL-c was determined to predict the 60-day survival. Patients with HDL-c ≥ 0.50 mmol/L showed a significantly higher 60-day survival rate than patients with HDL-c &amp;lt;0.50 mmol/L (70.9% vs 42.2%, p &amp;lt; 0.001.). Patients with HDL-c ≥ 0.50 mmol/L also showed longer overall survival (OS) (median OS: 346 days vs 34 days, p &amp;lt; 0.001). LDL-c showed no significant impacts on 60-day survival and OS. Dynamic data of HDL-c were available in 69.2% (117) of the patients. The median interval between the two tests was 18 (IQR: 15-25) days. The level of HDL-c after treatment increased in 80.3% (94/117) of the patients. The ratio of post-treatment HDL-c/baseline HDL-c was calculated and the median number was 1.67 (IQR: 1.05-2.48). The ratio was significantly lower in the patients with T/NK-cell malignancies than those with B-cell lymphomas (median 1.40 versus 1.97, p &amp;lt; 0.001). A ratio of 0.78 was determined as the best cutoff to predict the 60-day survival. Patients with a ratio&amp;lt;0.78 had significantly reduced 60-day survival (42.4% vs 76.6%, P=0.0035, Figure 1A) and OS (median 36 days vs 407 days, P=0.0001, Figure 1B). Then we divided these patients with available data into two groups based on baseline HDL-c and the ratio of post-treatment HDL-c/baseline HDL-c: Group 1 included patients with baseline HDL-c ≥ 0.5 mmol/L and Ratio ≥ 0.78, while others were classified as Group 2. Patients in Group 2 had significantly reduced 60-day survival (57.5% vs 87.6%, P=0.0003, Figure 1C) and OS (median 107 days vs not reached, P=0.0001, Figure 1D) than Group 1. Conclusion: Our study demonstrated serum HDL-c and its dynamic Change were robust and clinically feasible markers for predicting the outcomes of patients with lymphoma-associated HLH.

Moderate-intensity statin plus ezetimibe combination therapy versus high-intensity statin monotherapy according to baseline LDL-C levels: a prespecified subgroup analysis of RACING Trial

Abstract Aims To compare the effects of moderate-intensity statin plus ezetimibe combination therapy to high-intensity statin monotherapy based on baseline low-density lipoprotein cholesterol (LDL-C) levels. Methods and results In the RACING trial, 3780 atherosclerotic cardiovascular disease (ASCVD) patients were randomly assigned to moderate-intensity statin plus ezetimibe combination therapy or high-intensity statin monotherapy based on baseline LDL-C levels of &amp;lt;100 mg/dL (n=2817) or ≥100 mg/dL (n=963). In the prespecified analysis, the primary outcome (a composite of cardiovascular death, major cardiovascular event, or stroke at 3 years) and key secondary outcome (achievement of LDL-C &amp;lt;70 mg/dL) were reported according to baseline LDL-C levels. The occurrence of the primary outcome did not differ between the combination therapy and the monotherapy groups among those with lower and higher baseline LDL-C levels (8.6% versus 10.1%, hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.37 to 1.09; and 10.5% versus 9.3%, HR 1.13, 95% CI 0.76 to 1.70, respectively) without an interaction (P=0.232). The 1-, 2-, and 3-year achievement of LDL-C &amp;lt;70 mg/dL was greater in the combination therapy group, regardless of baseline LDL-C levels. For secondary safety outcomes, no significant interactions between the treatment strategies and baseline LDL-C levels were found. Conclusion Among ASCVD patients, the effect of moderate-intensity statin plus ezetimibe combination therapy was consistent across the baseline LDL-C levels for the 3-year composite of cardiovascular death, major cardiovascular event, or stroke, and even associated with greater achievement of LDL-C &amp;lt;70 mg/dL compared to high-intensity statin monotherapy.

Use of inclisiran in a real-world setting: results from the italian Cholinet registry

Abstract Background Real world data indicate that PCSK9 inhibitors (PCSK9i) are started in very high-risk patients at higher LDL cholesterol (LDL-C) values than those recommended by guidelines. Different reimbursement rules may have an impact on access to injectable therapy among different countries. In Italy, reimbursement of injectable lipid lowering therapies (LLT) (i.e., PCSK9i and inclisiran) has been recently allowed for very high risk patients with LDL-C levels &amp;gt;70 mg/dl while on statin/ezetimibe LLT or statin intolerant, and, thereafter, inclisiran has been introduced in clinical practice. No data are available on inclisiran real world use in Italy and on the impact of new reimbursement rules on patient access to inclisiran. Purpose Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry involving 21 Italian centers, designed to assess efficacy, safety, adherence and persistence, as well characteristics of very high risk patients with atherosclerotic CV disease (ASCVD) and/or familial hypercholesterolemia (FH) receiving inclisiran. Methods From November 2022 through February 2023, the Cholinet registry enrolled patients receiving inclisiran due to elevated LDL-C levels in Italian centers as part of their medical therapy. Baseline characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at follow-up. Results We enrolled 105 patients (14% FH, 30% female, mean age 64 years) receiving inclisiran according to standard clinical practice. 37 of them reached 3 months follow up (i.e., time of first reinjection dose) and none of them missed the reinjection dose. At the time of inclisiran first prescription median LDL-C was 96.6 mg/dl and reached 48.8 mg/dl at the time of 3 months observation (49% reduction). In patients with ASCVD median LDL-C at baseline was 90.4 mg/dL and 44.4 mg/dl at follow-up (51% reduction). In patients with FH median LDL-C at baseline was 177.4 mg/dL and 109.5 mg/dL at follow-up (38% reduction). Of 105 patients enrolled, 92 patients (88%) were on LLT. Heterogeneity was found on the LDL-C reduction across our cohort (Figure 1) (Shapiro-Wilk test p&amp;lt;0.05) that appeared to be influenced by background LLT (Kruskal-Wallis rank for previous PCSK9i exposure p=0.0028, for background LLT p=0.0435) (Figure 2), but not by baseline LDL-C levels (ANOVA p=0.06). LDL-C target was achieved in 21 (66%) of 32 patients receiving background LLT and in 2 (40%) of 5 patients who did not. No patient reported side effects. Conclusion These preliminary results from the Cholinet registry show that, in a context of facilitated reimbursement access, inclisiran is introduced at substantially lower baseline LDL-C values than previously reported for PCSK9i, reflecting a favorable change in clinical practice. Inclisiran effectively and safely reduces LDL-C in patients with ASCVD or FH, with some etherogeneity that was associated with background LLT.Kernel density plot, LDL-C % reductionStratified Kernel density plot

Improving statins effectiveness by targeting baseline LDL cholesterol in type 2 diabetes mellitus, a systematic review and meta-analysis

Abstract Background Although the guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D), it remains controversial whether their cardiovascular effectiveness depends on baseline LDL-Cholesterol (LDL-C) levels at the start of statin use. Purpose To determine whether the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality differ according to baseline LDL-C categories. Methods This study was registered in the PROSPERO database (CRD42022374004); and was performed according to the PRISMA statement. Through January 2022, Medline, Embase, and Web of science were systematically searched from inception. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to study if the association between statin use and the risk of all-cause mortality and MACE (a composite of myocardial infarction, hospitalization due to heart failure, stroke, and revascularization events) modified by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) &amp;lt;100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) ≥130 mg/dl (3.37 mmol/l) categories. Results A total of 11 cohort studies (n= 408,937 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.67 [95% CI 0.57 to 0.79]) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79]), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels of 130 mg/dl or higher had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29, 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and &amp;lt;100 mg/dl categories were respectively (0.66 [95% CI 0.53 to 0.82]) and (0.83 [95% CI [0.68, 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44, 1.02]). Statin use was associated with reductions in HRs of MACE (0.99 [95%CI, 0.98 to 1.00]; P = 0.11) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses. Conclusion The results of this study suggest that the greatest cardiovascular protective effects of statin therapy in patients with T2D are attributable to patients with baseline LDL-C levels of 130 mg/dl or higher in real-life settings of observational studies.

Early diagnosis and treatments in childhood are associated with better prognosis in patients with familial hypercholesterolemia

Abstract Objective The early diagnosis and treatment initiation for children with familial hypercholesterolemia (FH) has been recommended in guidelines. However, there is limited data on the impact of early treatments on the prognosis of children with FH. To investigate if the early initiation of lipid-lowering therapies among Japanese pediatric patients with FH reduced the occurrence of cardiovascular disease (CVD) events in them. Methods We retrospectively investigated the occurrence of CVD events (myocardial infarction, unstable angina, or coronary artery revascularization) in patients with FH (N = 1050, male/female = 490/560), including 106 children below 20 years. We compared a variety of phenotypes, including genetic backgrounds, other complications, LDL cholesterol, medical therapies, and their prognoses between the patients’ diagnoses before the age of 20 years (children, mean age = 15 years) and after that age (adults, mean age = 52 years). Overall, 290 patients (27.6%) had a history of prior CVD events. Results The median follow-up duration was 12.6 [9.5–17.9] years. The baseline LDL cholesterol level, 239 mg/dL, dropped to 112 mg/dL with the treatments. The Achilles tendon thickness was significantly lower in children than that of adults (7.2 vs. 8.9 mm, P &amp;lt; 0.001). Over the follow-up duration, 119 CVD events were observed. Importantly, no CVD event was observed in children despite their median LDL cholesterol level at follow-up being significantly higher than that of adults (122 vs. 111 mg/dL, P &amp;lt; 0.001). Conclusion The likelihood of CVD events in those with FH diagnosed and treated in childhood is low.

Abstract 12263: Inflammation and Cholesterol as Predictors of Cardiovascular Events and Risk Reduction With Bempedoic Acid Among Statin Intolerant Patients: An Analysis of the CLEAR Outcomes Trial

Introduction: Among contemporary statin-treated patients, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is a stronger predictor of future cardiovascular (CV) events and all-cause mortality than residual cholesterol risk assessed by low density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients is unknown but has implications for the choice of preventive therapies including bempedoic acid, an agent that reduces both LDLC and hsCRP. Methods: In the multi-national CLEAR-Outcomes trial, 13,970 statin-intolerant patients were randomly allocated 1:1 to 180 mg oral bempedoic acid daily or matching placebo and followed for incident myocardial infarction (MI), stroke, coronary revascularization, CV death, and all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse CV events after adjustment for traditional risk factors and treatment (bempedoic acid vs. placebo). Results: Baseline hsCRP was significantly associated with incident composite endpoint of MI, stroke, coronary revascularization, and CV death (highest vs lowest hsCRP quartile, HR=1.43, 95% CI 1.24-1.65), CV mortality (HR=2.00, 95% CI 1.53-2.61), and all-cause mortality (HR=2.21, 95% CI 1.79-2.73). By contrast, the relationship of baseline LDLC quartile (highest vs. lowest) to future CV events was smaller for the composite endpoint (HR=1.19, 95% CI 1.04-1.37) and neutral for CV mortality (HR 0.90, 95% CI 0.70-1.17) and all-cause mortality (HR 0.95, 95% CI 0.78-1.16) such that risks were high for those with elevated hsCRP irrespective of LDLC level. Compared to placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months and demonstrated similar efficacy in reducing major adverse CV events across all levels of hsCRP and LDLC. Interpretation: Among contemporary statin-intolerant patients, inflammation assessed by hsCRP was a stronger predictor of risk for future CV events and death than was hyperlipidemia assessed by LDLC. Compared to placebo, bempedoic acid had similar efficacy for reducing CV risk across hsCRP and LDLC strata.