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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
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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.
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Cost-Effectiveness of Lipid-Lowering Treatments in Young Adults.
Kohli-Lynch, CN, Bellows, BK, Zhang, Y, Spring, B, Kazi, DS, Pletcher, MJ, Vittinghoff, E, Allen, NB, Moran, AE
Journal of the American College of Cardiology. 2021;(20):1954-1964
Abstract
BACKGROUND Raised low-density lipoprotein cholesterol (LDL-C) in young adulthood (aged 18-39 years) is associated with atherosclerotic cardiovascular disease (ASCVD) later in life. Most young adults with elevated LDL-C do not currently receive lipid-lowering treatment. OBJECTIVES This study aimed to estimate the prevalence of elevated LDL-C in ASCVD-free U.S. young adults and the cost-effectiveness of lipid-lowering strategies for raised LDL-C in young adulthood compared with standard care. METHODS The prevalence of raised LDL-C was examined in the U.S. National Health and Nutrition Examination Survey. The CVD Policy Model projected lifetime quality-adjusted life years (QALYs), health care costs, and incremental cost-effectiveness ratios (ICERs) for lipid-lowering strategies. Standard care was statin treatment for adults aged ≥40 years based on LDL-C, ASCVD risk, or diabetes plus young adults with LDL-C ≥190 mg/dL. Lipid lowering incremental to standard care with moderate-intensity statins or intensive lifestyle interventions was simulated starting when young adult LDL-C was either ≥160 mg/dL or ≥130 mg/dL. RESULTS Approximately 27% of ASCVD-free young adults have LDL-C of ≥130 mg/dL, and 9% have LDL-C of ≥160 mg/dL. The model projected that young adult lipid lowering with statins or lifestyle interventions would prevent lifetime ASCVD events and increase QALYs compared with standard care. ICERs were US$31,000/QALY for statins in young adult men with LDL-C of ≥130 mg/dL and US$106,000/QALY for statins in young adult women with LDL-C of ≥130 mg/dL. Intensive lifestyle intervention was more costly and less effective than statin therapy. CONCLUSIONS Statin treatment for LDL-C of ≥130 mg/dL is highly cost-effective in young adult men and intermediately cost-effective in young adult women.
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Serum folate modified the association between low-density lipoprotein cholesterol and carotid intima-media thickness in Chinese hypertensive adults.
Ding, C, Bi, C, Lin, T, Hu, L, Huang, X, Liu, L, Liu, C, Song, Y, Tang, G, Wang, B, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(12):2303-2311
Abstract
BACKGROUND AND AIMS While folate is known for its importance in cardiovascular health, it is unknown whether folate status can modify the association between low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (CIMT). We aimed to investigate this question in a Chinese hypertensive population, who are at high-risk of low folate and atherosclerosis. METHODS AND RESULTS This report included 14,970 hypertensive adults (mean age 64.5 years; 40.3% male) from the China Stroke Primary Prevention Trial (CSPPT) and analyzed the fasting serum LDL-C and folate, and CIMT data obtained at the last follow-up visit. LDL-C was calculated using the Friedewald equation. Serum folate levels were measured by chemiluminescent immunoassay. CIMT was measured by ultrasound. Non-parametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the LDL-C-CIMI relationship and effect modification by folate. Consistent with graphic plots, multivariate linear regression showed that LDL-C levels were independently and positively associated with CIMT (β = 7.69, 95%CI: 5.76-9.62). More importantly, the relationship between LDL-C and CIMT was significantly attenuated with increasing serum folate levels (1st tertile: β = 10.06, 95%CI: 6.67-13.46; 2nd tertile: β = 6.81, 95%CI: 3.55-10.07; 3rd tertile: β = 5.96, 95%CI: 2.55-9.36; P-interaction = 0.045). Subgroup analyses showed the association between LDL-C and CIMT across serum folate tertiles was robust among various strata (all P-interaction >0.05). CONCLUSIONS Among Chinese hypertensive adults, the serum folate levels could modify the association between LDL-C and CIMT. Our findings, if further confirmed, have important clinical implications.
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Efficacy and safety of bempedoic acid for prevention of cardiovascular events and diabetes: a systematic review and meta-analysis.
Wang, X, Zhang, Y, Tan, H, Wang, P, Zha, X, Chong, W, Zhou, L, Fang, F
Cardiovascular diabetology. 2020;(1):128
Abstract
BACKGROUND Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the prevention of cardiovascular events and diabetes is lacking. Thus, we aim to evaluate the benefit and safety of bempedoic acid use for the prevention of cardiovascular events and diabetes. METHODS We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials with no language restriction from inception until March 3, 2020. Pairs of reviewers independently identified randomized controlled trials comparing the use of bempedoic acid with placebo or no treatment for primary prevention of cardiovascular events in statin-intolerant patients with hypercholesterolemia. The primary outcomes were major adverse cardiac events, and percent change in LDL-C. RESULTS We identified 11 trials including a total of 4391 participants. Bempedoic acid use was associated with a reduction in composite cardiovascular outcome (RR 0.75, 95% CI 0.56-0.99; I2 = 0%). Bempedoic acid reduced LDL-C levels (MD - 22.91, 95% CI - 27.35 to - 18.47; I2 = 99%), and similarly reduced CRP levels (MD -24.70, 95% CI - 32.10 to - 17.30; I2 = 53%). Bempedoic acid was associated with a reduction in rates of new-onset or worsening diabetes (RR 0.65, 95% CI 0.44-0.96; I2 = 23%). CONCLUSIONS Bempedoic acid in patients with hypercholesterolemia was associated with a lower risk of cardiovascular events and diabetes.
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Evinacumab for Homozygous Familial Hypercholesterolemia.
Raal, FJ, Rosenson, RS, Reeskamp, LF, Hovingh, GK, Kastelein, JJP, Rubba, P, Ali, S, Banerjee, P, Chan, KC, Gipe, DA, et al
The New England journal of medicine. 2020;(8):711-720
Abstract
BACKGROUND Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P<0.001); the between-group least-squares mean absolute difference in the LDL cholesterol level was -132.1 mg per deciliter (95% CI, -175.3 to -88.9; P<0.001). The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null-null variants (-43.4% vs. +16.2%) and in those with non-null variants (-49.1% vs. -3.8%). Adverse events were similar in the two groups. CONCLUSIONS In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks. (Funded by Regeneron Pharmaceuticals; ELIPSE HoFH ClinicalTrials.gov number, NCT03399786.).
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Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study.
Jin, JL, Zhang, HW, Cao, YX, Liu, HH, Hua, Q, Li, YF, Zhang, Y, Wu, NQ, Zhu, CG, Xu, RX, et al
Cardiovascular diabetology. 2020;(1):45
Abstract
BACKGROUND Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM. METHODS A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated. RESULTS A total of 464 MACEs were documented. Both Kaplan-Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24-2.70, p < 0.05). However, no significant association was observed for high sdLDL plus Pre-DM or NGR. CONCLUSIONS The present study firstly indicated that elevated levels of plasma sdLDL were associated with increased risk of MACEs among DM patients with proven CAD, suggesting that sdLDL may be useful for CAD risk stratification in DM.
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Prognostic significance of serum cystatin C in acute ischemic stroke patients according to lipid component levels.
Zhu, Z, Zhong, C, Xu, T, Wang, A, Peng, Y, Xu, T, Peng, H, Chen, CS, Wang, J, Li, Q, et al
Atherosclerosis. 2018;:146-151
Abstract
BACKGROUND AND AIMS Serum cystatin C (CysC) is associated with the risk of ischemic stroke and may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and functional outcome in ischemic stroke patients remains unclear, and whether lipid component level influences the relationship between them has not been studied. METHODS A total of 3348 ischemic patients from China Antihypertensive Trial in Acute Ischemic Stroke were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. The primary outcome was poor functional outcome (modified Rankin Scale score ≥3) at one year after ischemic stroke. Secondary outcomes were death, stroke recurrence, vascular events and combination of the aforementioned outcomes. RESULTS The association between eGFRCysC and primary outcome was appreciably modified by low-density lipoprotein cholesterol (LDL-C) (pinteraction = 0.048). Low eGFRCysC was associated with primary outcome only in ischemic stroke patients with LDL-C ≥4.14 mmol/l rather than all patients. The multivariable adjusted odds ratio (95% confidence interval) of poor functional outcome associated with low eGFRCysC was 3.94 (1.04-14.98) and a positive linear dose-response relationship between them was observed among patients with LDL-C ≥4.14 mmol/l (p for linearity = 0.021). Subgroup analyses further confirmed these associations. There was no association between eGFR based on serum creatinine and poor functional outcome of stroke. CONCLUSIONS Low eGFRCysC may be an independent predictor for 1-year poor functional outcome in ischemic stroke patients with LDL-C ≥4.14 mmol/l. Further studies are needed to replicate our findings and to clarify the potential mechanisms.
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Non-HDL-C is a Better Predictor for the Severity of Coronary Atherosclerosis Compared with LDL-C.
Zhang, Y, Wu, NQ, Li, S, Zhu, CG, Guo, YL, Qing, P, Gao, Y, Li, XL, Liu, G, Dong, Q, et al
Heart, lung & circulation. 2016;(10):975-81
Abstract
BACKGROUND Recent guidelines recommended both low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) are the primary target of lipid modulating therapy. However, which lipid measure is most closely related to the severity of coronary atherosclerosis has not yet been assessed. METHODS We studied 1757 consecutive subjects undergoing coronary angiography who were not receiving any lipid-lowering therapy. Low-density lipoprotein cholesterol was measured directly, and non-HDL-C was calculated. The severity of coronary stenosis was determined using the Gensini Score (GS) system. RESULTS In the overall population, LDL-C and non-HDL-C were all dramatically increased according to the quartiles of GS (p<0.001, both). In patients with coronary atherosclerosis (n=1097), non-HDL-C (r=0.138, p<0.001) was more closely related to GS than LDL-C (r=0.113, p<0.001) tested by Spearman correlation analysis. Multivariate logistic regression analysis suggested that non-HDL-C (OR=1.326, 95% CI 1.165-1.508, p<0.001) was slightly superior to LDL-C (OR=1.286, 95% CI 1.130-1.463, p<0.001) in predicting high GS after adjusting for potential confounders. Among patients with LDL-C less than the median, discordant non-HDL-C could not provide extra value in predicting high GS (OR=0.759, 95% CI 0.480-1.201). However, among patients with LDL-C greater than or equal to the median, the cardiovascular risk was overestimated for patients with discordant non-HDL-C (OR=0.458, 95% CI 0.285-0.736). CONCLUSIONS Our data support the use of non-HDL-C ahead of LDL-C in predicting the severity of coronary atherosclerosis, especially among patients with LDL-C greater than or equal to the median.
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Analysis of Lipoprotein Subfractions in Chinese Han Patients with Stable Coronary Artery Disease.
Xu, RX, Zhang, Y, Ye, P, Chen, H, Li, YF, Hua, Q, Guo, YL, Li, XL, Li, S, Dong, Q, et al
Heart, lung & circulation. 2015;(12):1203-10
Abstract
BACKGROUND The relation of lipoprotein subfractions with stable coronary artery disease (CAD) has not been fully investigated in the Chinese Han population. METHODS Four-hundred-and-thirteen consecutive patients without any lipid-lowering drug treatment were investigated. Patients were classified into two groups according to the angiographic results: CAD group (n=293) and non-CAD group (n=120). The high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions were analysed using the Quantimetrix Lipoprint system. RESULTS The data showed that the large HDL-cholesterol (HDL-C) level, large HDL subfraction percentage, and mean LDL particle size were significantly lower, while the small HDL-C level and HDL subfraction percentage, intermediate and small LDL-cholesterol (LDL-C) levels, and LDL subfraction percentages were higher in the CAD group compared with those in the non-CAD group. Interestingly, our results suggested that the small HDL-C level and HDL subfraction percentage as well as mean LDL particle size were independently associated with the presence of CAD assessed by logistic regression analysis (OR=1.136, 95%CI=1.018-1.268, p=0.022; OR=1.076, 95%CI=1.021-1.134, p=0.007; OR=0.946, 95%CI=0.898-0.997, p=0.040; respectively). CONCLUSIONS Similar to previous Western population studies, our data suggested a clear association between the lipoprotein subfractions and stable CAD presented as higher small HDL subfraction and smaller mean LDL particle size in Chinese Han patients.
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Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.
Zanchetti, A, Liu, L, Mancia, G, Parati, G, Grassi, G, Stramba-Badiale, M, Silani, V, Bilo, G, Corrao, G, Zambon, A, et al
Journal of hypertension. 2014;(9):1741-50
Abstract
BACKGROUND AND OBJECTIVES It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.