Well-controlled Low-density Lipoprotein Cholesterol Levels Research Articles

Association between triglyceride glucose index and adverse clinical outcomes in patients with acute myocardial infarction and LDL-C≤1.8 mmol/L who underwent percutaneous coronary intervention: a prospective cohort study.

Recently, the triglyceride glucose (TyG) index has emerged as a reliable predictive indicator for adverse outcomes of cardiovascular disease. However, the roles of the TyG index in patients with acute myocardial infarction (AMI) and low-density lipoprotein cholesterol (LDL-C)≤1.8 mmol/L after percutaneous coronary intervention (PCI) remain unclear. A total of 599 patients diagnosed with AMI and LDL-C ≤ 1.8 mmol/L at the 1-month follow-up after PCI were consecutively enrolled between January 2017 and January 2020. The patients were subsequently divided into three groups based on tertiles of the TyG index. The parameters, including the TyG index, were compared to explore the risk factors associated with major adverse cardiovascular and cerebrovascular events (MACCEs) during the 1-year follow-up. Sixty-nine patients (11.5%) with 90 MACCEs were recorded during the 1-year follow up, including 13 patients (8.6%) in the Tertile 1 group, 36 (12.0%) in the Tertile 2 group, and 20 (13.4%) in the Tertile 3 group. Patients with a higher TyG index had a significantly increased incidence of MACCEs compared to those with a lower TyG index (22.1% vs. 14.0% vs. 9.9%, p=0.010). Kaplan-Meier analysis demonstrated that patients with a higher TyG index had a significantly lower probability of survival without MACCEs. Furthermore, a binary logistic regression model indicated that the TyG index was the only independent predictor for MACCEs in these patients. A higher TyG index was associated with a higher incidence of MACCEs in patients with AMI and well-controlled LDL-C levels after PCI. This suggests that the TyG index can serve as a predictive indicator for adverse cardiovascular outcomes in these patients.

Independent association of PCSK9 with platelet reactivity in subjects without statin or antiplatelet agents.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could predict cardiovascular event in patients with well-controlled LDL-C levels, suggesting an LDL-independent mechanism of PCSK9 on the cardiovascular system. Accumulating evidence suggests PCSK9 might be associated with increased platelet reactivity. This study aimed to assess the relationship between PCSK9 levels and platelet reactivity in subjects not taking statins or antiplatelet agents. A cross-sectional study was conducted to investigate the independent contribution of PCSK9 to platelet activity by controlling for the potential confounding factors. The study population included 89 subjects from a health examination centre who underwent routine annual health check-ups or had an examination before a selective operation. Subjects taking statins or antiplatelet agents were excluded. Adenosine diphosphate (ADP)-induced platelet aggregation was determined by PL-11 platelet analyzer using impedance aggregometry and plasma PCSK9 levels were determined using an ELISA. Serum Lipid profile was assessed by measuring the concentration of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), with low-density lipoprotein cholesterol (LDL-C) being directly measured using enzymatic techniques. The association between PCSK9 and platelet reactivity was investigated. The study subjects were composed of 53 males and 36 females with an average age of 55 (±11) years old. The univariate correlation analysis showed significant correlation between ADP-induced maximal aggregation rate (MAR) and PCSK9 (r = 0.55, p < 0.001) as well as TC (r = 0.23, p = 0.028), LDL-C (r = 0.27, p < 0.001), and PLT (r = 0.31, p = 0.005). Being male (41.2% vs. 46.6, p = 0.04) and smoking (37.4 vs. 46.2%, p = 0.016) were associated with lower ADP-induced MAR than being female and non-smoking. However, there is no correlation between PCSK9 and AA-induced platelet maximal aggregation rate (r = 0.17, p = 0.12). Multiple regression analysis suggested that PCSK9 contributed independently to ADP-induced maximal aggregation rate (β = 0.08, p = 0.004) after controlling for the effect of TC, LDL-C, PLT, being male, and smoking. PCSK9 is positively associated with platelet reactivity, which may partly account for the beneficial effect of PCSK9 inhibition in reducing the risk of major adverse cardiovascular events after acute coronary syndrome (ACS).

Optimal Low-Density Lipoprotein Cholesterol Levels in Adults Without Diabetes Mellitus: A Nationwide Population-Based Study Including More Than 4 Million Individuals From South Korea.

BackgroundAlthough the strong association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) is well-known, the threshold LDL-C level at which the risk of CVD begins to increase in individuals without diabetes mellitus (DM) remains unknown. We aimed to evaluate the association between incident CVD and serum LDL-C levels with or without statin use in individuals without DM.MethodsWe identified 4,182,117 individuals without previous CVD who underwent a health screening examination in 2009 and 2011 from the Korean National Health Insurance Cohort database. The primary endpoint was a composite of cardiovascular deaths, myocardial infarction (MI) cases, and ischemic stroke cases.ResultsDuring the median follow-up of 6 years, there were 51,961 CVD events that included 17,392 MI cases, 33,779 ischemic stroke cases, and 2,039 cardiovascular deaths. The LDL-C levels that were associated with an increased risk of CVD were ≥100 mg/dL in non-statin users and ≥130 mg/dL in statin users. However, even in individuals with lower LDL-C levels, all those with fasting plasma glucose (FPG) levels ≥110 mg/dL had a significantly higher risk of CVD.ConclusionsWe demonstrated that LDL-C levels ≥100 mg/dL were correlated with an increased risk of CVD in individuals without DM and a history of CVD. We found that a glucose, cholesterol interaction increased CVD risk, and modestly elevated FPG levels (110–125 mg/dL) were associated with a higher CVD risk even in individuals with well-controlled LDL-C levels.

Mild Malnutrition Contributes the Greatest to the Poor Prognosis in Coronary Artery Disease With Well-Controlled Low-Density Lipoprotein Cholesterol Levels: A 4,863 Chinese Cohort Study.

Background: Previous studies reported that patients with coronary artery disease (CAD) and well-controlled baseline LDL-C (<1.8 mmol/L) still had higher long-term all-cause mortality. However, no study has been conducted to explore the independent risk factors for long-term mortality. In addition, there also was no study evaluating the population attributable risk (PAR) of independent risk factors in combination with their prevalence and relative risk. Therefore, we aimed to identify the independent risk factors and estimate their PAR in patients with CAD and well-controlled baseline LDL-C (<1.8 mmol/L).Methods: We analyzed 4,863 consecutive CAD patients with well-controlled baseline LDL-C admitted to Guangdong Provincial People's Hospital in China from January 2007 to December 2018. Independent risk factors for long-term all-cause death were evaluated through stepwise approach and multivariable Cox regression analysis. PAR of independent risk factors was calculated with their hazard ratio and prevalence among our cohort.Results: The overall mortality was 16.00% (n = 778) over a median follow-up period of 5.93 years. Independent risk factors for all-cause death included malnutrition, age ≥75 years, congestive heart failure (CHF), chronic kidney disease (CKD) and atrial fibrillation. Among these risk factors of interest, the hazard ratio (HR) of severe malnutrition was the highest (HR 2.82, 95% CI: 1.86–4.26), and the PAR of mild malnutrition was the highest (19.49%, 95% CI: 0.65–36.01%).Conclusion: Malnutrition, age ≥75 years, CHF, CKD and atrial fibrillation were independent predictors for long-term all-cause mortality in CAD patients with well-controlled LDL-C levels. Considering prevalence of these risk factors, more attention should be paid to the occurrence of mild malnutrition for these patients.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04407936.

Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites.

Patients with well-controlled low-density lipoprotein cholesterol levels, but persistent high triglycerides, remain at increased risk for cardiovascular events as evidenced by multiple genetic and epidemiologic studies, as well as recent clinical outcome trials. While many trials of low-dose ω3-polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown mixed results to reduce cardiovascular events, recent trials with high-dose ω3-PUFAs have reignited interest in ω3-PUFAs, particularly EPA, in cardiovascular disease (CVD). REDUCE-IT demonstrated that high-dose EPA (4 g/day icosapent-ethyl) reduced a composite of clinical events by 25% in statin-treated patients with established CVD or diabetes and other cardiovascular risk factors. Outcome trials in similar statin-treated patients using DHA-containing high-dose ω3 formulations have not yet shown the benefits of EPA alone. However, there are data to show that high-dose ω3-PUFAs in patients with acute myocardial infarction had reduced left ventricular remodelling, non-infarct myocardial fibrosis, and systemic inflammation. ω3-polyunsaturated fatty acids, along with their metabolites, such as oxylipins and other lipid mediators, have complex effects on the cardiovascular system. Together they target free fatty acid receptors and peroxisome proliferator-activated receptors in various tissues to modulate inflammation and lipid metabolism. Here, we review these multifactorial mechanisms of ω3-PUFAs in view of recent clinical findings. These findings indicate physico-chemical and biological diversity among ω3-PUFAs that influence tissue distributions as well as disparate effects on membrane organization, rates of lipid oxidation, as well as various receptor-mediated signal transduction pathways and effects on gene expression.

Changes in triglyceride, HDL-C, and non-HDL-C levels in patients with acute coronary syndrome.

Changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels have been linked to residual cardiovascular risk, whereas non-HDL-C levels have been shown to be more predictive of cardiovascular risk than are low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the impact of HDL-C, TG, and non-HDL-C levels on acute coronary syndrome (ACS) risk with on-target LDL-C levels. In all, 424 Caucasian patients aged over 50years who had LDL-C levels below 3.4mmol/l with a first or subsequent ACS event were enrolled in a multicenter, retrospective study. Lipid samples were collected within 4days after the cardiovascular event. The subjects of the age-matched, gender-balanced control group (n= 443) had LDL-C levels below 3.4mmol/l and were free of cardiovascular diseases. Patients with ACS had significantly higher TG and lower HDL-C levels compared with the control patients; however, we did not find any significant difference regarding non-HDL-C levels between the two groups. In regression analysis, the risk of coronary heart disease increased significantly with 1standard deviation (SD) increase in TG and 1SD decrease in HDL-C levels. High TG and low HDL-C levels may contribute to residual cardiovascular risk in patients with well-controlled LDL-C levels; however, non-HDL-C levels at admission did not seem to be predictive for patients with ACS. Detection and treatment of secondary lipid targets such as high TG and low HDL-C levels may be important for the prevention of cardiovascular diseases.

Nonoptimal high-density lipoprotein cholesterol levels are highly prevalent in patients presenting with acute coronary syndromes and well-controlled low-density lipoprotein cholesterol levels

Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for coronary artery disease. For this study, nonoptimal HDL-C is defined as less than 40 mg/dL for male patients and less than 50 mg/dL for female patients. Even when low-density lipoprotein cholesterol (LDL-C) and non-HDL-C goals are met, significant risk for subsequent cardiovascular events remains in patients with acute coronary syndrome (ACS). This study is a prospective, observational study to determine the prevalence of low HDL-C levels in 250 consecutive patients presenting with ACS who have well-controlled LDL-C levels. This was an institutional review board-approved, prospective, observational study in which we evaluated consecutive patients admitted to the adult general cardiology service with a diagnosis of ACS. One hundred nine (44%) patients had LDL-C levels less than 100 mg/dL on admission. Of those patients, 90 (83%) had a nonoptimal HDL-C. Interestingly, a majority of patients, 94 (86%), had non-HDL-C levels at target. At discharge, approximately one half of eligible patients were started on therapy to increase their HDL-C levels. In conclusion, nonoptimal HDL-C levels are highly prevalent in patients presenting with ACS and reasonably controlled LDL-C and non-HDL-C levels.

Peripheral Arterial Tonometry for Risk Stratification in Men With Coronary Artery Disease

Coronary artery disease (CAD) risk is not fully revealed by traditional risk factors. Identification of a simple, noninvasive tool that allows for detection of high-risk CAD patients and can be applied in large populations and clinical settings would prove valuable. We sought to test the hypothesis that peripheral arterial tonometry (PAT) would be associated with residual risk in men with CAD. In this study, finger PAT was used to measure pulse wave amplitude (PWA) during reactive hyperemia (RH) and taken as a measure of microvascular endothelial function in 42 men with stable CAD and well controlled low-density lipoprotein cholesterol (LDL-C) levels. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA(2)) were measured and used to reclassify men into high-risk (elevated hs-CRP and Lp-PLA(2)), moderate-risk (either elevated hs-CRP or Lp-PLA(2)), or low-risk (low hs-CRP and Lp-PLA(2)) groups. PWA-RH was significantly lower in the high-risk group (1.3 +/- 0.04) compared to the moderate-risk (1.6 +/- 0.07, P < 0.05) and low-risk (2.0 +/- 0.1, P < 0.05) groups. According to binary logistic regression, PWA-RH was a significant predictor of high-risk status among men with CAD (P < 0.05). Measurement of peripheral microvascular endothelial function with PAT may be able to distinguish high-risk men from moderate- and low-risk men with stable CAD and well-controlled LDL-C levels and thus aid in residual risk stratification in this at risk cohort.

Extended-release niacin reduces LDL particle number without changing total LDL cholesterol in patients with stable CAD

The importance of the number of circulating low-density lipoprotein (LDL) cholesterol particles, in addition to total LDL level, has been increasingly recognized. The effects of extended-release niacin (ERN) on LDL particle numbers have not been studied. To evaluate ERN's effects on LDL particle numbers. Fifty-four patients with stable coronary artery disease (CAD) and well-controlled LDL levels were randomly assigned to 3 months of ERN (1 g/day) or placebo in addition to their baseline medications. Lipoprotein particle number was analyzed by proton nuclear magnetic resonance spectroscopy at baseline and after 3 months. Compared to baseline, the addition of ERN had no significant effect on total LDL cholesterol levels; however, ERN decreased the number of medium and small LDL particles (P < .005). After 3 months, ERN decreased the number of medium and small LDL particles compared to placebo-treated patients (P < .05). ERN raised HDL cholesterol levels by 2.7%, significantly increased the number of large HDL particles (P < .001), and decreased the number of small HDL particles (P = .027) compared to placebo. There were no significant changes in lipid values or particle numbers in the placebo-treated patients. In patients with stable coronary artery disease and well-controlled LDL cholesterol levels, ERN reduced the number of circulating particles of the more atherogenic subtypes of LDL, despite having no effect on total LDL cholesterol levels. ERN also favorably altered the number of HDL particles. ERN-induced alterations in lipoprotein particle numbers may contribute to its anti-atherosclerotic effects, and these effects may not be evident from the standard lipid profile.

Abstract 5144: Extended-Release Niacin Reduces LDL-C Particle Number Even In The Absence Of Changes In Total LDL-C Levels

Introduction: The importance of the number of circulating low-density lipoprotein cholesterol (LDL-C) particles, in addition to the total level of LDL-C is increasingly recognized. The effects of Extended Release Niacin (ERN) on LDL-C particle number have not been studied. The primary objective of this study was to evaluate ERN’s effects on LDL-C particle number. ERN’s effect on high-density lipoprotein cholesterol (HDL-C) particle number was a secondary objective. Hypothesis : In patients with stable coronary artery disease (CAD) and LDL-C at goal, the addition of ERN will favorably alter LDL-C particle number. Methods: 60 patients with stable CAD and well-controlled LDL-C levels were randomly assigned to 3 months of ERN (1g/d) or placebo in addition to their baseline medications. Particle number was analyzed by proton nuclear magnetic resonance spectroscopy at baseline and after 3 months. Results: Baseline and follow up lipid values are shown in Table . Compared to baseline, while ERN had no significant effect on total LDL-C levels, it significantly decreased the mean number of medium and small very small LDL-C particles (p=0.005). The percent change in each of these particle numbers was significantly greater in the ERN group compared to placebo as well (p&lt;0.05 for each) ERN therapy raised HDL-C levels and also significantly shifted from small to large HDL-C particles (p&lt;0.001). There were no significant changes in lipid values or particle numbers in the placebo-treated patients ( Table ). Conclusion: In patients with stable CAD and well-controlled LDL-C levels, ERN significantly reduced the number of circulating particles of the more atherogenic subtypes of LDL-C, despite having no effect on total LDL-C levels. ERN also favorably altered particle numbers of HDL-C. These findings suggest that ERN-induced alterations in particle number may contribute to its anti-atherosclerotic effects, and that these effects may not be evident from the standard lipid profile.