-
1.
Influence of lipoproteins and antiplatelet agents on vein graft patency 1 year after coronary artery bypass grafting.
Zhu, J, Zhu, Y, Zhang, M, Xue, Q, Hu, J, Liu, H, Wang, R, Wang, X, Zhao, Q
The Journal of thoracic and cardiovascular surgery. 2022;(3):1030-1039.e4
-
-
Free full text
-
Abstract
OBJECTIVE It remains unclear whether aggressive low-density lipoprotein cholesterol (LDL-C) management (<1.8 mmol/L) can slow the process of vein graft stenosis. This study aimed to explore the impact of baseline LDL-C levels on vein graft patency in patients on ticagrelor with or without aspirin 1 year after coronary artery bypass grafting (CABG). METHODS This was a post hoc analysis of the DACAB (Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery) trial (NCT02201771), a randomized controlled trial (ticagrelor + aspirin or ticagrelor vs aspirin) of patients undergoing CABG in China. The study subjects were stratified as LDL-low (baseline LDL-C <1.8 mmol/L, 148 patients with 430 vein grafts) versus LDL-high (baseline LDL-C ≥1.8 mmol/L, 352 patients with 1030 vein grafts). The primary outcome was the 1-year vein graft patency (Fitzgibbon grade A) assessed by coronary computed tomographic angiography or coronary angiography. RESULTS Baseline/1-year LDL-C were 1.4/1.6 and 2.6/2.4 mmol/L in the LDL-low and LDL-high subgroups, respectively. Regardless of antiplatelet regimen, no significant inter-subgroup difference was observed for 1-year graft patency (LDL-low: 83.8% [359/430 grafts]; LDL-high: 82.3% [848/1030 grafts]; adjusted OR for non-patency [ORadj], 0.96; 95% confidence interval [CI], 0.62-1.50, P = .857). For both subgroups, the 1-year graft patency rates were greater with ticagrelor + aspirin versus aspirin (LDL-low: ORadj, 0.41; 95% CI, 0.17-0.97; LDL-high: ORadj, 0.38; 95% CI, 0.20-0.71; inter P = .679). CONCLUSIONS In general, baseline LDL-C is not associated with 1-year vein graft patency after CABG. Regardless of the baseline LDL-C levels, ticagrelor + aspirin was superior to aspirin alone in maintaining vein graft patency. The primary factor causing early vein graft disease might not be atherosclerosis but thrombosis.
-
2.
High Triglyceride-Glucose Index is Associated with Poor Cardiovascular Outcomes in Nondiabetic Patients with ACS with LDL-C below 1.8 mmol/L.
Zhang, Y, Ding, X, Hua, B, Liu, Q, Gao, H, Chen, H, Zhao, XQ, Li, W, Li, H
Journal of atherosclerosis and thrombosis. 2022;(2):268-281
-
-
Free full text
-
Abstract
AIM: To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L. METHODS A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2]. RESULTS Compared with the TyG index <8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p=0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p=0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p=0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p=0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index <8.33 group (8.9% vs. 5.0%, p=0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02-2.75; p=0.043]. CONCLUSIONS In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.
-
3.
Influence of the LDL-Receptor Genotype on Statin Response in Heterozygous Familial Hypercholesterolemia: Insights From the Canadian FH Registry.
Roy, G, Couture, P, Genest, J, Ruel, I, Baass, A, Bergeron, J, Brisson, D, Brunham, LR, Cermakova, L, Gaudet, D, et al
The Canadian journal of cardiology. 2022;(3):311-319
Abstract
BACKGROUND Whether low-density lipoprotein (LDL) receptor (LDLR) residual activity influences the LDL-lowering effect of statins in heterozygous familial hypercholesterolemia (HeFH) remains unclear. The objective of this study was to investigate the relationship between the LDLR genotype and statin-induced LDL cholesterol (LDL-C) reductions in HeFH. METHODS A total of 615 individuals with HeFH (receptor-defective [RD] genotype: n = 226; receptor-negative [RN] genotype: n = 389) from 7 lipid clinics across Canada who initiated statin monotherapy were included in this retrospective longitudinal study. Statin-induced reductions in LDL-C among individuals with RD and RN genotypes were compared with the use of linear models. RESULTS There were 334 women and 281 men with a mean untreated LDL-C concentrations of 6.97 ± 1.65 mmol/L. Untreated and on-statin LDL-C levels where higher among patients with an RN genotype: untreated: RN 7.24 (95% confidence interval [CI] 6.98-7.50) mmol/L vs RD 6.70 (95% CI 6.41-6.98) mmol/L (P = 0.0002); on-statin: RN 4.50 (95% CI 4.31-4.70) vs RD 4.05 (95% CI 3.84-4.26) mmol/L (P = 0.0004). After adjustments for age, sex, smoking status, untreated LDL-C concentrations, statin type and dose, as well as the clinic where the patients were treated, the LDL-C-lowering effect of statins was significantly weaker for individuals with an RN mutation than for individuals with an RD mutation: RN: -31.1% (95% CI -34.7% to -27.4) vs RD -36.5% (95% CI -40.4% to -32.6%); P < 0.0001. The LDLR genotype was the strongest nonmodifiable independent correlate of statin-induced LDL-C reductions (R2 = 2.3%; P = 0.0001). CONCLUSION The LDLR genotype is significantly associated with statin-induced reductions in LDL-C concentrations in HeFH.
-
4.
Association of Serum Low-Density Lipoprotein, High-Density Lipoprotein, and Total Cholesterol With Development of Knee Osteoarthritis.
Schwager, JL, Nevitt, MC, Torner, J, Lewis, CE, Matthan, NR, Wang, N, Sun, X, Lichtenstein, AH, Felson, D, ,
Arthritis care & research. 2022;(2):274-280
-
-
Free full text
-
Abstract
OBJECTIVE Studies suggest an association between elevated total serum cholesterol, particularly low-density lipoprotein (LDL), and osteoarthritis (OA). The present study was undertaken to evaluate the association between total cholesterol, LDL, and high-density lipoprotein (HDL) and risk of knee OA. METHODS We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee radiographs and magnetic resonance images (MRIs) were obtained, and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined 2 sets of patients: those developing radiographic OA, and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of cartilage loss and synovitis on MRI and of knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index scale. We carried out logistic regression adjusting for age, sex, body mass index, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures, and we performed sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL, or low HDL increased risk. RESULTS We studied 337 patients with incident symptomatic OA and 283 patients with incident radiographic OA. The mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL, nor HDL showed a significant association with radiographic or symptomatic OA. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis, or worsening knee pain. CONCLUSION Our data do not support an association between total cholesterol, LDL, or HDL with OA outcomes.
-
5.
Role of Bempedoic Acid in Clinical Practice.
Ballantyne, CM, Bays, H, Catapano, AL, Goldberg, A, Ray, KK, Saseen, JJ
Cardiovascular drugs and therapy. 2021;(4):853-864
-
-
Free full text
-
Abstract
Many patients do not achieve optimal low-density lipoprotein cholesterol (LDL-C) levels with statins alone; others are unable to tolerate statin therapy. Additional non-statin treatment options including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bile acid sequestrants are often necessary to further reduce the risk of atherosclerotic cardiovascular disease. This review provides practical guidance as to the use of bempedoic acid to lower LDL-C and includes direction as to which patients may benefit and advice for safety monitoring during treatment. Bempedoic acid, a new class of agent, is a prodrug converted to bempedoyl-CoA by very long-chain acyl-CoA synthetase 1, an enzyme with high expression in the liver but that is undetectable in the skeletal muscle. Bempedoic acid inhibits the enzyme adenosine triphosphate (ATP)-citrate lyase, which lies two steps upstream from β-hydroxy β-methylglutaryl-CoA reductase in the cholesterol biosynthesis pathway. In clinical trials conducted in patients with or at risk for atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia, bempedoic acid in combination with statins and/or ezetimibe significantly reduced LDL-C, apolipoprotein B, and high-sensitivity C-reactive protein compared with placebo. Bempedoic acid is generally well tolerated with no clinically meaningful increase in muscle-related symptoms relative to placebo, even in patients taking maximally tolerated statins. A small increase in serum uric acid (mean increase 0.8 mg/dL) is the most noteworthy adverse effect. Bempedoic acid provides an effective and generally well-tolerated medication to further reduce LDL-C in patients taking maximally tolerated statins or manage LDL-C levels in those who are unable to take statins. The potential for a reduced incidence of major cardiovascular events with bempedoic acid is being investigated in the CLEAR Outcomes trial, with results expected in 2023.
-
6.
Predictive value of a reduction in the level of high-density lipoprotein-cholesterol in patients with non-small-cell lung cancer undergoing radical resection and adjuvant chemotherapy: a retrospective observational study.
Luo, F, Zeng, KM, Cao, JX, Zhou, T, Lin, SX, Ma, WJ, Yang, YP, Zhang, ZH, Lu, FT, Huang, Y, et al
Lipids in health and disease. 2021;(1):109
Abstract
BACKGROUND Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. METHODS NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. RESULTS Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). CONCLUSIONS Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.
-
7.
LDL cholesterol and atherosclerosis: The evidence.
Guijarro, C, Cosín-Sales, J
Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis. 2021;:25-32
Abstract
The lipid theory of atherosclerosis dates back more than a century. Despite this, some authors have questioned the relevance of hypercholesterolaemia in its development. Multiple experimental, epidemiological, and clinical evidence underpins this association. Atherosclerotic cardiovascular disease remains as the major cause of mortality in the world. Recent genetic studies of Mendelian randomisation and randomised clinical trials aimed at LDL cholesterol reduction, are summarised in this article. They, unequivocally ratify the aetiological role of LDL cholesterol in the development of atherosclerosis. Thus, LDL cholesterol lowering is the cornerstone of lipid lowering therapy for the reduction of cardiovascular complications of atherosclerosis.
-
8.
Clinical Efficacy and Safety of Alirocumab After Acute Coronary Syndrome According to Achieved Level of Low-Density Lipoprotein Cholesterol: A Propensity Score-Matched Analysis of the ODYSSEY OUTCOMES Trial.
Schwartz, GG, Gabriel Steg, P, Bhatt, DL, Bittner, VA, Diaz, R, Goodman, SG, Jukema, JW, Kim, YU, Li, QH, Manvelian, G, et al
Circulation. 2021;(11):1109-1122
-
-
Free full text
-
Abstract
BACKGROUND Recent international guidelines have lowered recommended target levels of low-density lipoprotein cholesterol (LDL-C) for patients at very high risk for major adverse cardiovascular events (MACE). However, uncertainty persists whether additional benefit results from achieved LDL-C levels below the conventional targets. Inferences from previous analyses are limited because patients who achieve lower versus higher LDL-C on lipid-lowering therapy differ in other characteristics prognostic for MACE and because few achieved very low LDL-C levels. To overcome these limitations, we performed a propensity score-matching analysis of the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) which compared alirocumab with placebo in 18 924 patients with recent acute coronary syndrome receiving intensive or maximum-tolerated statin treatment. METHODS Patients on alirocumab were classified in prespecified strata of LDL-C achieved at 4 months of treatment: <25 (n=3357), 25 to 50 (n=3692), or >50 mg/dL (n=2197). For each stratum, MACE (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) after month 4 was compared in patients receiving placebo with similar baseline characteristics and adherence by using 1:1 propensity score matching. RESULTS Across achieved LDL-C strata of the alirocumab group, patients differed by baseline LDL-C, lipoprotein(a), use of intensive statin therapy, study medication adherence, and other demographic, medical history, biometric, and laboratory criteria. After propensity score matching, characteristics were similar in corresponding patients of the alirocumab and placebo groups. Treatment hazard ratio, 95% CI, and absolute risk reduction (number per 100 patient-years) for MACE were similar in those with achieved LDL-C <25 mg/dL (hazard ratio, 0.74 [95% CI, 0.62-0.89]; absolute risk reduction, 0.92) or 25 to 50 mg/dL (hazard ratio, 0.74 [95% CI, 0.64-0.87]; absolute risk reduction, 1.05). Patients with achieved LDL-C >50 mg/dL had poorer adherence and derived less benefit (hazard ratio, 0.87 [95% CI, 0.73-1.04]; absolute risk reduction, 0.62). No safety concerns were associated with a limited period of LDL-C levels <15 mg/dL. CONCLUSIONS After accounting for differences in baseline characteristics and adherence, patients treated with alirocumab who achieved LDL-C levels <25 mg/dL had a reduction in the risk of MACE that was similar to that of patients who achieved LDL-C levels of 25 to 50 mg/dL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.
-
9.
The Effect of Long-Term Atorvastatin Therapy on Carotid Intima-Media Thickness of Children With Dyslipidemia.
Karapostolakis, G, Vakaki, M, Attilakos, A, Marmarinos, A, Papadaki, M, Koumanidou, C, Alexopoulou, E, Gourgiotis, D, Garoufi, A
Angiology. 2021;(4):322-331
Abstract
Carotid intima-media thickness (cIMT) has been proposed as an early marker of subclinical atherosclerosis in high risk children. Children with heterozygous familial hypercholesterolemia have greater cIMT than matched healthy controls or their unaffected siblings. Statin therapy may delay the progression of cIMT, although long-term studies in children are scarce. We evaluated the effect of atorvastatin treatment on cIMT in children with dyslipidemia. We studied 81 children/adolescents, 27 with severe dyslipidemia (low-density lipoprotein cholesterol [LDL-C] ≥190 mg/dL) and 54 sex- and age-matched healthy controls; LDL-C ≤ 130 mg/dL and lipoprotein (a), Lp(a), ≤30 mg/dL. In the children with dyslipidemia, cIMT was measured twice, before and on treatment (18.2 ± 7.7 months). Anthropometric data, a full lipid profile, liver, kidney, and thyroid function were evaluated. Males with dyslipidemia had a greater cIMT than male controls after adjustment for other factors (P = .049). In addition, a nonstatistically significant decrease in cIMT was observed after treatment (P = .261). Treatment with atorvastatin resulted in a significantly improved lipid profile. Females with dyslipidemia had a significantly thinner cIMT than males. Children with normal and high Lp(a) levels had similar cIMT values. In conclusion, treatment with atorvastatin had a beneficial effect on the lipid profile and cIMT progression in children with severe dyslipidemia.
-
10.
Bempedoic Acid: A New Drug for an Old Problem.
Nguyen, D, Du, N, Sulaica, EM, Wanat, MA
The Annals of pharmacotherapy. 2021;(2):246-251
Abstract
OBJECTIVE To review the pharmacology, pharmacokinetics, safety, and efficacy of bempedoic acid for low-density lipoprotein cholesterol (LDL-C) reduction. DATA SOURCES A PubMed search was conducted from January 2000 to June 15, 2020, using the keyword bempedoic acid for phase III clinical trials published in the English language. STUDY SELECTION AND DATA EXTRACTION Articles related to the Food and Drug Administration (FDA) approval of bempedoic acid and other trials relating to the safety and efficacy of this drug were included. DATA SYNTHESIS The findings from this review show that bempedoic acid is a safe and effective option for lowering LDL-C levels in patients requiring LDL-C lowering for primary or secondary prevention of cardiovascular events. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE Statin therapy remains the mainstay of treatment for both primary and secondary prevention. However, many patients cannot tolerate statin therapy because of statin-associated muscle symptoms. Bempedoic acid may be a reasonable adjunct for LDL-C reduction, though further evaluation of cardiovascular outcomes with bempedoic acid in this population is needed. CONCLUSIONS The recent FDA approval of bempedoic acid offers an additional option for lowering LDL-C levels in patients with atherosclerotic cardiovascular disease or heterozygous familial hyperlipidemia. Additional data regarding effect on long-term cardiovascular outcomes with bempedoic acid are currently being studied.