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1.
Is it time to reconcile HDL with cardiovascular diseases and beyond? An update on a paradigm shift.
Martinez, LO, Ingueneau, C, Genoux, A
Current opinion in lipidology. 2020;(5):302-304
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2.
HDL cholesterol is an independent predictor of β-cell function decline and incident type 2 diabetes: A longitudinal study.
Fiorentino, TV, Succurro, E, Marini, MA, Pedace, E, Andreozzi, F, Perticone, M, Sciacqua, A, Perticone, F, Sesti, G
Diabetes/metabolism research and reviews. 2020;(4):e3289
Abstract
BACKGROUND Experimental evidence indicates that high-density lipoprotein (HDL) may stimulate glucose uptake and improve β-cell function. The aim of this study was to evaluate whether lower levels of HDL may affect the risk to develop type 2 diabetes. METHODS Incident rate of type 2 diabetes and changes in insulin sensitivity and β-cell function over 5.5-year follow-up were examined in 670 non-diabetic subjects stratified in tertiles according to basal HDL levels. RESULTS As compared to the highest tertile of HDL, individuals with lower levels of HDL have an increased risk to develop type 2 diabetes independently from several cardiometabolic risk factors (odds ratio: 2.88, 95% confidence interval: 1.05-7.91), and exhibited a greater deterioration of β-cell function, estimated by the disposition index, over 5.5-year follow-up. Conversely, changes in Matsuda index of insulin sensitivity over the follow-up were not significantly different amongst the three HDL groups. In a multivariable regression analysis model including age, sex, waist circumference, triglycerides, total cholesterol, C-reactive protein, fasting and 2-hour post-load glucose, family history of type 2 diabetes and smoking habit, HDL concentration at baseline was an independent predictor of β-cell function decline over the follow-up (β = .30, P = .0001). Mediation analysis showed that the association between lower HDL levels at baseline and increased risk of incident diabetes was mediated by β-cell function deterioration during the follow-up (t = -3.32, P = .001). CONCLUSIONS Subjects with lower levels of HDL have an increased risk to develop type 2 diabetes likely due to a greater β-cell function decline over time.
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3.
Effects of Living High-Training Low and High on Body Composition and Metabolic Risk Markers in Overweight and Obese Females.
Gao, H, Xu, J, Zhang, L, Lu, Y, Gao, B, Feng, L
BioMed research international. 2020;:3279710
Abstract
This study examined the effects of 4 weeks of living high-training low and high (LHTLH) under moderate hypoxia on body weight, body composition, and metabolic risk markers of overweight and obese females. Nineteen healthy overweight or obese females participated in this study. Participants were assigned to the normoxic training group (NG) or the LHTLH group (HG). The NG participants lived and trained at sea level. The HG participants stayed for approximately 10 hours in a simulated 2300 m normobaric state of hypoxia for six days a week and trained for 2 hours 3 times a week under the same simulated hypoxia. The interventions lasted for 4 weeks. All groups underwent dietary restriction based on resting metabolic rate. The heart rate of the participants was monitored every ten minutes during exercise to ensure that the intensity was in the aerobic range. Compared with the preintervention values, body weight decreased significantly in both the NG and the HG (-8.81 ± 2.09% and -9.09 ± 1.15%, respectively). The fat mass of the arm, leg, trunk, and whole body showed significant reductions in both the NG and the HG, but no significant interaction effect was observed. The percentage of lean soft tissue mass loss in the total body weight loss tended to be lower in the HG (27.61% versus 15.94%, P=0.085). Between the NG and the HG, significant interaction effects of serum total cholesterol (-12.66 ± 9.09% versus -0.05 ± 13.36%,) and apolipoprotein A1 (-13.66 ± 3.61% versus -5.32 ± 11.07%, P=0.042) were observed. A slight increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the HG (1.12 ± 12.34%) but a decrease was observed in the NG (-11.36 ± 18.91%). The interaction effect of HDL-C between NG and HG exhibited a significant trend (P=0.055). No added effects on serum triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), or APO-B were observed after 4 weeks of LHTLH. In conclusion, 4 weeks of LHTLH combined with dietary restriction could effectively reduce the body weight and body fat mass of overweight and obese females. Compared with training and sleeping under normoxia, no additive benefit of LHTLH on the loss of body weight and body fat mass was exhibited. However, LHTLH may help to relieve the loss of lean soft tissue mass and serum HDL-C.
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4.
A U-shaped association between the LDL-cholesterol to HDL-cholesterol ratio and all-cause mortality in elderly hypertensive patients: a prospective cohort study.
Yu, Y, Li, M, Huang, X, Zhou, W, Wang, T, Zhu, L, Ding, C, Tao, Y, Bao, H, Cheng, X
Lipids in health and disease. 2020;(1):238
Abstract
BACKGROUND The low-density lipoprotein cholesterol/high-density lipoprotein- cholesterol (LDL-C/HDL-C) ratio is an excellent predictor of cardiovascular disease (CVD). However, previous studies linking the LDL-C/HDL-C ratio to mortality have yielded inconsistent results and been limited by short follow-up periods. Therefore, the aim of the present study was to determine whether the LDL-C/HDL-C ratio could be an effective predictor of all-cause mortality in elderly hypertensive patients. METHODS A total of 6941 hypertensive patients aged 65 years or older who were not treated with lipid-lowering drugs were selected from the Chinese Hypertension Registry for analysis. The endpoint of the study was all-cause mortality. The relationship between the LDL-C/HDL-C ratio and all-cause mortality was determined using multivariate Cox proportional hazards regression, smoothing curve fitting (penalized spline method), subgroup analysis and Kaplan-Meier survival curve analysis. RESULTS During a median follow-up of 1.72 years, 157 all-cause deaths occurred. A U-shaped association was found between the LDL-C/HDL-C ratio and all-cause mortality. Patients were divided according to the quintiles of the LDL-C/HDL-C ratio. Compared to the reference group (Q3: 1.67-2.10), patients with both lower (Q1 and Q2) and higher (Q4 and Q5) LDL-C/HDL-C ratios had higher all-cause mortality (< 1.67: HR 1.81, 95% CI: 1.08-3.03; ≥2.10: HR 2.00, 95% CI: 1.18-3.39). Compared with the lower and higher LDL-C/HDL-C ratio groups, patients with LDL-C/HDL-C ratios of 1.67-2.10 had a significantly higher survival probability (log-rank P = 0.038). CONCLUSIONS The results suggest that there is a U-shaped association between the LDL-C/HDL-C ratio and all-cause mortality. Both lower and higher LDL-C/HDL-C ratios were associated with increased all-cause mortality in elderly hypertensive patients.
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5.
Lower levels of high-density lipoprotein cholesterol are associated with increased cardiovascular events in patients with acute coronary syndrome.
Nakazawa, M, Arashi, H, Yamaguchi, J, Ogawa, H, Hagiwara, N
Atherosclerosis. 2020;:21-28
Abstract
BACKGROUND AND AIMS This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events. METHODS The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. The entire cohort was divided into three groups according to tertiles of HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, HDL-C >43, <53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups. RESULTS The primary endpoint event occurred in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively, and its incidence was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19-1.9; p = 0.001). Irrespective of the treatment regimen, Group 1 had significantly higher rates of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12-2.22; p = 0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05-1.98; p = 0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles. Multivariate analysis revealed that lower body mass index, prevalence of diabetes mellitus, higher levels of high-sensitivity C reactive protein at baseline, and lower levels of HDL-C at 3-month follow-up were independent predictors of the incidence of primary endpoint. CONCLUSIONS Lower levels of HDL-C at 3-month follow-up are independently associated with higher incidence of cardiovascular events in ACS patients receiving contemporary lipid-lowering therapy.
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6.
Lower HDL-C levels are associated with higher expressions of CD16 on monocyte subsets in coronary atherosclerosis.
Xiang, Y, Liang, B, Zhang, X, Zheng, F
International journal of medical sciences. 2020;(14):2171-2179
Abstract
Background: Increased expressions of CD16 on classical monocytes precede their transition to intermediate monocytes. Thus far, the influence of lipids on the expression of CD14 and CD16 on monocyte subsets in coronary atherosclerosis (CA) remains unclear. The aim of this study was to investigate the underlying association between blood lipids and the expression of CD14 and CD16 on monocyte subsets. Methods: This study enrolled 112 healthy controls and 110 CA patients. Monocyte subsets [CD14++CD16- (classical), CD14++CD16+ (intermediate) and CD14+CD16++ (non-classical)] were analyzed by flow cytometry. Median fluorescent intensity (MFI) was used to evaluate the expression levels of CD14 and CD16 on monocyte subsets. Results: Compared with the control group, the expression of CD16 was significantly increased on all three monocyte subsets in the patient group. Correlation analysis revealed that serum HDL-C was inversely associated with the expression of CD16 on intermediate monocytes after Bonferroni correction in the control group. In addition, a significant decrease in classical monocytes and an increase in intermediate monocytes were detected in patients. In linear regression analysis, intermediate monocytes showed an inverse association with serum HDL-C in the control group. Although CD14 was correlated with serum TC and HDL-C, there was no statistical difference in CD14 expression between the two groups. Conclusion: Low serum HDL-C may induce upregulation of CD16 on classical monocytes, which may in turn lead to the increase of intermediate monocytes in coronary atherosclerosis patients.
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7.
Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease.
Boden, WE, Miller, MG, McBride, R, Harvey, C, Snabes, MC, Schmidt, J, McGovern, ME, Fleg, JL, Desvigne-Nickens, P, Anderson, T, et al
American heart journal. 2020;:65-76
Abstract
BACKGROUND Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.
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8.
HDL-apoA-I kinetics in response to 16 wk of exercise training in men with nonalcoholic fatty liver disease.
Whyte, MB, Shojaee-Moradie, F, Sharaf, SE, Cuthbertson, DJ, Kemp, GJ, Barrett, M, Jackson, NC, Herring, RA, Wright, J, Thomas, EL, et al
American journal of physiology. Endocrinology and metabolism. 2020;(6):E839-E847
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise (n = 15), or conventional lifestyle advice (n = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; P < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); P = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.
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9.
Intra-Abdominal Fat and High Density Lipoprotein Cholesterol Are Associated in a Non-Linear Pattern in Japanese-Americans.
Song, SO, Hwang, YC, Kahn, SE, Leonetti, DL, Fujimoto, WY, Boyko, EJ
Diabetes & metabolism journal. 2020;(2):277-285
Abstract
BACKGROUND We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots. METHODS We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined using multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials. RESULTS Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 cm², and 1.67±0.43 mg/dL, 74.4±46.6 cm² and differed significantly by gender for both comparisons (P<0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF: β=-0.1012, P<0.001; IAF²: β=0.0008, P<0.001). SCF was also negatively and linearly associated with HDL-C (β=-0.4919, P=0.001). CONCLUSION HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association.
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10.
Effect of isotretinoin treatment on the inflammatory markers in patients with acne vulgaris: can monocyte/HDL be a new indicator for inflammatory activity of isotretinoin treatment?
Kutlu, Ö
Cutaneous and ocular toxicology. 2020;(1):67-70
Abstract
Background: Oral isotretinoin (ISO) can effect markers of inflammation in patients with acne vulgaris. To our knowledge, there are no data on the relationship between ISO and monocyte to HDL cholesterol ratio (MHR). In this study, it is aimed to examine the effect of the ISO treatment on the MHR and other inflammatory markers in patients with acne vulgaris.Materials and methods: In this study, 89 out of 120 patients with severe/very severe acne vulgaris according to the Global Acne Grading Scale who received at least 3 months of ISO treatment were evaluated. The complete blood counts including mean levels of mean platelet volume, plateletcrit (PTC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), MHR, and serum biochemistry panel were evaluated before and after ISO treatment.Results: The mean platelet value, NLR, and PLR levels underwent a statistically significant decrease after ISO treatment (p < 0.05) while MHR increased significantly 3 months after ISO treatment (p = 0.017). The mean platelet value, NLR, and PLR levels were 9.56 ± 1.05, 2.15 ± 0.81, and 142.45 ± 48.33 before treatment while were 9.32 ± 1.45, 1.90 ± 0.99, and 127.94 ± 41.38 after treatment, respectively. On the other hand, MHR was 9.76 ± 4.27 and 10.86 ± 4.12 before and after treatment, respectively.Conclusions: In this study, we found that ISO may have both inflammatory and anti-inflammatory effects by using MPV, PTC, NLR, PLR, and MHR. The inflammatory effects of ISO may be associated with possible inflammatory diseases. MHR can be used as a novel marker to investigate the inflammatory effect of the ISO.