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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids.
Jhun, MA, Mendelson, M, Wilson, R, Gondalia, R, Joehanes, R, Salfati, E, Zhao, X, Braun, KVE, Do, AN, Hedman, ÅK, et al
Nature communications. 2021;(1):3987
Abstract
Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.
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Association of Clinician Knowledge and Statin Beliefs With Statin Therapy Use and Lipid Levels (A Survey of US Practice in the PALM Registry).
Lowenstern, A, Navar, AM, Li, S, Virani, SS, Goldberg, AC, Louie, MJ, Lee, LV, Peterson, ED, Wang, TY
The American journal of cardiology. 2019;(7):1011-1018
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Abstract
Guideline implementation requires clinician knowledge but may be influenced by pre-existing beliefs and biases. We assessed the association of these clinician factors with lipid management following the release of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines. In the PALM registry, 774 clinicians completed a survey to assess their knowledge of the 2013 American College of Cardiology/American Heart Association guidelines, belief in statin benefit, and statin safety concerns. The association of these factors with statin use, statin dosing, and low-density lipoprotein cholesterol (LDL-C) levels were assessed in the 6,839 patients treated by these clinicians between May and November 2015. Overall, 63.9% of clinicians responded to at least 3 out of 4 hypothetical scenarios in concordance with guideline recommendations (good tested knowledge), 88.4% reported belief in statin benefit, and 15.4% raised concerns about statin safety. Belief in statin benefit was more prevalent among cardiologists, who represented 48.8% of the clinicians surveyed, and concerns regarding statin safety were higher among noncardiologists and clinicians in an academic setting. Guideline knowledge was not associated with a difference in statin use (74.1% vs 73.8%, p = 0.84) and achievement of LDL-C level <100 mg/dl (54.7% vs 52.4%, p = 0.07). However, patients treated by clinicians who reported belief in statin benefit were more likely to receive guideline-recommended statin intensity (41.9% vs 36.9%, p = 0.03), whereas patients treated by clinicians expressing statin safety concerns were less likely receive statins of at least guideline-recommended intensity (36.8% vs 42.5%, p = 0.001) and to achieve an LDL-C <100 mg/dl (44.1% vs 56.1%, p <0.001); the latter persisted after multivariable adjustment (odds ratio 0.75, 95% confidence interval 0.63 to 0.89). In conclusion, clinician beliefs regarding benefits and risks of statins were significantly associated with guideline adherence and patients' achieved LDL-C levels, whereas clinician knowledge of guideline recommendations was not.
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Characteristics of lipid profiles and lipid control in patients with diabetes in a tertiary hospital in Southwest China: an observational study based on electronic medical records.
Hou, Q, Yu, C, Li, S, Li, Y, Zhang, R, Zheng, T, Ma, Y, Wang, M, Su, N, Wu, T, et al
Lipids in health and disease. 2019;(1):13
Abstract
BACKGROUND Diabetes is often accompanied by dyslipidemia. Lipid control is very important in the management of diabetes. There are limited real world data on the lipid control in diabetic inpatients in southwest China. METHODS An observational study was conducted to assess the characteristics of lipid profiles and lipid control. Diabetic patients from February 2009 to December 2013 at West China Hospital of Sichuan University were identified. RESULTS A total of 56,784 inpatients were included and 85.9% of them had at least one lipid panel. The proportions of inpatients with optimal low-density lipoprotein cholesterol (LDL-C) level (< 2.59 mmol/L), optimal triglyceride (TG) level (< 1.70 mmol/L), optimal high-density lipoprotein cholesterol (HDL-C) level (men ≥1.04 mmol/L; women ≥1.30 mmol/L) and optimal non-high-density lipoprotein cholesterol (non-HDL-C) level (< 3.37 mmol/L) were 61.1, 64.6, 49.9 and 64.5%, respectively. Only 23.1% of inpatients obtained optimal levels for all the above four lipid parameters. Of diabetic inpatients with ischemic heart disease, the proportions of inpatients with optimal LDL-C level (< 1.81 mmol/L), optimal TG level (< 1.70 mmol/L), optimal HDL-C level (men ≥1.04 mmol/L; women ≥1.30 mmol/L) and optimal non-HDL-C level (< 2.59 mmol/L) were 38.0, 66.3, 48.1 and 48.7%, respectively. Of diabetic inpatients with cerebrovascular disease, the proportions were 28.3, 64.8, 49.9 and 38.1%, respectively. Older people and men were more likely to obtain optimal lipid levels. However, inpatients between 46 and 64 years were least likely to obtain optimal LDL-C levels. CONCLUSIONS The lipid control of diabetic inpatients in southwest China is worrisome. Individualized strategies of lipid management should be taken to bridge the gap between the recommendations of clinical guidelines and the real situation of clinical practice.
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The effects of red yeast rice dietary supplement on blood pressure, lipid profile, and C-reactive protein in hypertension: A systematic review.
Xiong, X, Wang, P, Li, X, Zhang, Y, Li, S
Critical reviews in food science and nutrition. 2017;(9):1831-1851
Abstract
Interest is increasing regarding the potential health effects of red yeast rice (RYR) consumption, which is described as a "natural statin" in China. This review aims to evaluate the efficacy of RYR on blood pressure (BP), lipid profile, and C-reactive protein (CRP) in treating hypertension. Seven electronic databases including the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and the Wanfang database were searched. To investigate the role of RYR for hypertension, randomized controlled trials for the use of RYR either as monotherapy or in combination with conventional medicine versus placebo, no intervention, or conventional medicine for hypertension were identified. A total of 21 trials containing 4558 patients were analyzed, the majority of which had low methodological quality. "RYR plus conventional therapy" exhibited significant lowering effects on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and CRP but exhibited no significant effect on systolic BP, diastolic BP, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with "placebo plus conventional therapy." "RYR plus conventional therapy" showed significant lowering effects on systolic BP, TC, LDL-C, and CRP but no effect on diastolic BP, TG, and HDL-C compared with "placebo plus conventional therapy." No significant difference in BP and lipid profile between "RYR plus conventional therapy" and "statins plus conventional therapy" was observed. "RYR plus statins" appeared to be more effective in lowering BP, TC, TG, and LDL-C but without a significant difference in HDL-C compared to statins. No serious adverse events were reported. The results of this meta-analysis suggested some supportive but limited evidence regarding RYR for hypertension. Further rigorously designed trials are warranted before RYR could be recommended to hypertensive patients.
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Fibrinogen and the Severity of Coronary Atherosclerosis among Adults with and without Statin Treatment: Lipid as a mediator.
Zhang, Y, Zhu, CG, Guo, YL, Li, S, Xu, RX, Dong, Q, Li, JJ
Heart, lung & circulation. 2016;(6):558-67
Abstract
BACKGROUND It has been proposed that plasma fibrinogen is associated with lipid levels and increased cardiovascular risk. However, the interrelationship has not been well-elucidated. We hypothesise that lipids may be potential mediators. METHODS We enrolled 4748 consecutive subjects scheduled for coronary angiography in this study. The severity of coronary atherosclerosis was assessed by Gensini score (GS). By principle component analysis, a multi-marker lipid index was extracted weighting the coefficients of six atherogenic lipid parameters: total cholesterol (TC), low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein (apo) B, apoB/apoA1, and TC/HDL-C ratio. Moreover, using mediation analysis, the relationship between fibrinogen and lipids with high GS was evaluated. RESULTS Fibrinogen was positively associated with GS after adjustment (β=0.100, p<0.001). We stratified our analyses by statin use status and found that subjects in the upper fibrinogen tertiles had higher levels of atherogenic lipid parameters irrespective of statin status (p<0.001, all). Significantly, we observed a synergistic effect of fibrinogen and concurrent elevated lipid index for high GS. The adjusted odds ratios were greater in participants who had high fibrinogen levels and also high lipid index compared to those with low lipid index [on statin: 1.725(1.258-2.364) vs. 1.261(0.962-1.652); not on statin: 2.197(1.450-3.328) vs. 1.166(0.417-3.258)]. Specifically, mediation analysis indicated that around 24% of the effect of fibrinogen on high GS was mediated by lipid index, which was attenuated to 13% by statin status. CONCLUSIONS The increased risk of fibrinogen on coronary atherosclerosis appeared to be enhanced by the high atherogenic lipid levels, which mediated around 24% of this effect.
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Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis.
Song, Y, Zhu, L, Richa, M, Li, P, Yang, Y, Li, S
Lipids in health and disease. 2015;:32
Abstract
BACKGROUND Studies of the association between the apolipoprotein C3 gene (APOC3) rs5128 polymorphism and plasma levels of apolipoprotein C3 (APOC3) and lipids have reported apparently conflicting findings. This meta-analysis aimed to investigate the associations of the rs5128 polymorphism with fasting APOC3 and lipid levels. METHODS The following information was abstracted for each study: ethnicity, age, sex, health condition, sample size, genotyping and lipid assay methods, mean and standard deviation or standard error by genotypes for APOC3 and lipid variables. There were 42 eligible studies with 23846 subjects included in this meta-analysis. A dominant model was used for this meta-analysis. RESULTS The results showed that the carriers of the variant allele G had higher levels of APOC3 [standardized mean difference (SMD): 0.22, 95% confidence interval (CI): 0.12-0.31, P<0.00001], triglycerides (TG) (SMD: 0.33, 95% CI: 0.23-0.44, P<0.00001), total cholesterol (TC) (SMD: 0.15, 95% CI: 0.09-0.22, P<0.00001), and low-density lipoprotein cholesterol (LDL-C) (SMD: 0.11, 95% CI: 0.04-0.17, P=0.001) than the non-carriers. No significant association between the APOC3 rs5128 polymorphism and lower levels of high-density lipoprotein cholesterol (HDL-C) was detected under the dominant model (SMD: -0.03, 95% CI: -0.06-0.01, P=0.156). CONCLUSIONS The results from the present meta-analysis demonstrate a significant association between the APOC3 rs5128 polymorphism and higher levels of APOC3, TG, TC and LDL-C, but further studies are needed to elucidate the underlying mechanisms.
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Amelioration of lipid abnormalities by α-lipoic acid through antioxidative and anti-inflammatory effects.
Zhang, Y, Han, P, Wu, N, He, B, Lu, Y, Li, S, Liu, Y, Zhao, S, Liu, L, Li, Y
Obesity (Silver Spring, Md.). 2011;(8):1647-53
Abstract
Recent data have revealed that oxidative products and inflammatory mediators are increased in the insulin-resistant states of obesity and type 2 diabetes mellitus (T2DM). Obese patients with impaired glucose tolerance (IGT) are at high risk for developing T2DM and have high incidence of dyslipidemia. α-Lipoic acid (ALA) is a potent antioxidant with insulin sensitizing activity. However, it is not clear whether ALA is effective on lipid parameters in humans. This study has investigated 22 obese subjects with IGT (obese-IGT), 13 of whom underwent 2-week ALA treatment, 600 mg intravenously once daily. Before and after the treatment, euglycemic-hyperinsulinemic clamps were used to measure insulin sensitivity. Meanwhile, plasma lipids, oxidative products, and chronic inflammatory markers were measured. After treatment of ALA in obese-IGT patients, insulin sensitivity was improved, insulin sensitivity index (ISI) impressively enhanced by 41%. Plasma levels of free fatty acids (FFAs), triglyceride (TG), total cholesterol (T-Chol), low density lipoprotein-cholesterol (LDL-Chol), small dense LDL-Chol (sd-LDL), oxidized LDL-Chol (ox-LDL-Chol), very low density lipoprotein-cholesterol (VLDL-Chol) were all significantly decreased (P < 0.01). At the same time, both plasma oxidative products (malondialdehyde (MDA), 8-iso-prostaglandin) and inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)) were remarkably decreased (P < 0.01), while adiponectin was increased (P < 0.01). There are significant negative correlations between ISI and plasma FFAs, sd-LDL-Chol, ox-LDL-Chol, MDA, 8-iso-prostaglandin, TNF-α, and IL-6, and positive correlations with HDL-Chol and adiponectin in obese-IGT patients. The results indicate that short-term treatment with ALA can improve insulin sensitivity and plasma lipid profile possibly through amelioration of oxidative stress and chronic inflammatory reaction in obese patients with IGT.