Abstract 97: Association of the Serum Myeloperoxidase/High-Density Lipoprotein Particle Ratio and Incident Cardiovascular Events in a Multi-Ethnic Population: Observations From the Dallas Heart Study

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Htet W Khine ◽  
John F Teiber ◽  
Robert W Haley ◽  
Amit Khera ◽  
Anand Rohatgi

Introduction: Myeloperoxidase (MPO) promotes oxidation of lipoproteins whereas high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO can induce dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We hypothesized that increased serum levels of MPO indexed to HDL particle concentration would be associated with an adverse phenotype with increased CVD risk and tested this hypothesis in a large multiethnic population free of CVD at baseline. Methods: Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD (57% women, 49% black). The associations of the MPO/HDLp ratio with incident ASCVD (first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors (age, sex, race, hypertension, smoking, total cholesterol, and statin use). The median follow-up period was 9.4 years. Results: MPO/HDLp was associated directly with total cholesterol, C-reactive protein, interleukin 18, and body mass index, and inversely with PON1 arylesterase activity, HDL-C, and HDL size. In adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total CVD (aHR, 1.91, 95% CI 1.27-2.85). Conclusion: Increasing MPO indexed to HDL particle concentration at baseline is associated with increased risk of incident CVD events in a population initially free of CVD, reflecting increased inflammation and decreased PON1 arylesterase activity. This is the first report of the MPO/HDLp ratio in a large human cohort. Further studies are warranted investigating MPO/HDLp as a biomarker of HDL metabolism and CVD risk.

2015 ◽  
Vol 42 (9) ◽  
pp. 1652-1660 ◽  
Author(s):  
Christina Gkolfinopoulou ◽  
Efstratios Stratikos ◽  
Dimitris Theofilatos ◽  
Dimitris Kardassis ◽  
Paraskevi V. Voulgari ◽  
...  

Objective.Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with increased risk of cardiovascular disease (CVD). High-density lipoprotein (HDL) exerts a series of antiatherogenic properties and protects from CVD. We evaluated whether HDL antiatherogenic properties are impaired in patients with AS.Methods.HDL (apoB-depleted serum) was isolated from 35 patients with AS and 35 age- and sex-matched controls. We measured the antioxidant capacity of HDL, the ability of HDL to induce cholesterol efflux, the activity of HDL-associated enzymes paraoxonase-1 (PON1) and myeloperoxidase (MPO), as well as the ability of HDL to induce Akt kinase activation.Results.HDL from patients with AS had decreased antioxidant capacity and decreased ability to promote cholesterol efflux from macrophages compared to controls. HDL-associated PON1 activity was lower and HDL-associated MPO activity higher in patients with AS compared to controls. Higher MPO activity correlated positively with lower antioxidant capacity of HDL in patients with AS. In addition, HDL from patients with AS had impaired endothelial Akt kinase activating properties that were inversely correlated with the MPO/PON1 ratio and positively correlated with the cholesterol efflux capacity of HDL.Conclusion.HDL from patients with AS displays impaired antiatherogenic properties. Attenuation of HDL properties may constitute a link between AS and CVD.


2010 ◽  
Vol 163 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Elena Succurro ◽  
Franco Arturi ◽  
Alessandro Grembiale ◽  
Fiorella Iorio ◽  
Irma Laino ◽  
...  

AimsLow IGF1 levels have been associated with an increased cardiovascular risk. It is unknown however whether IGF1 mediates the atherosclerotic process by modulating high-density lipoprotein cholesterol (HDL-C) independently from confounders. To address this issue, we evaluated the association between IGF1 levels and HDL-C in nondiabetic subjects.MethodsA cross-sectional analysis was used in the context of the CAtanzaro MEtabolic RIsk factors Study. One thousand and four participants (aged 20–69 years), for whom HDL-C and IGF1 measurements were available, were eligible for the study.ResultsAfter adjusting for gender and age, IGF1 levels were positively correlated with HDL-C, and negatively correlated with body mass index (BMI), waist circumference, blood pressure (BP), triglyceride, fasting insulin, and homeostasis model assessment (HOMA). In a logistic regression model adjusted for age and gender, IGF1 in the lowest tertile (<125 ng/ml) was associated with an increased risk of having low HDL-C (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.4–3.0; P=4×10−5) compared with the highest tertile (>186 ng/ml). When BMI, waist circumference, total cholesterol, triglyceride, and HOMA index were added to the model, IGF1 remained significantly associated with increased risk of low HDL-C (OR 1.52, 95% CI 1.01–2.31; P=0.04). A stepwise multivariate regression analysis in a model including age, gender, BMI, total cholesterol, triglycerides, IGF1, HOMA, and BP showed that the variables significantly associated with HDL-C were gender (P<0.0001), triglycerides (P<0.0001), total cholesterol (P<0.0001), BMI (P<0.0001), IGF1 levels (P<0.0001), and HOMA (P=0.001), accounting for 32.6% of its variation.ConclusionsThese data provide evidence that IGF1 may be an independent modulator for HDL-C in nondiabetic individuals.


2012 ◽  
Vol 8 (4) ◽  
pp. 398-404
Author(s):  
M Aryal ◽  
A Poudel ◽  
B Satyal ◽  
P Gyawali ◽  
B R Pokheral ◽  
...  

Background Cardiovascular disease (CVD), is the primary cause of morbidity and mortality in patients with diabetes and have approximately - two to four times higher CVD rate than adult without diabetes. Low density lipoprotein cholesterol (LDL-C) is primarily used as the marker of cardiovascular risk in diabetes despite its several limitations. Although several newer markers of CVD are emerging, no marker has been established in Nepal. Objectives The study was designed to evaluate the non-high-density-lipoprotein- cholesterol(Non-HDL-C) and Total Cholesterol to High density lipoprotein cholesterol (TC:HDL-C ratio) as CVD risk marker in diabetes mellitus. Methods The study was conducted in the Department of Bbiochemistry, Kathmandu University School of Medical Sciences. The study comprised of 76 diabetic subjects and 60 non-diabetic subjects. The anthropometric and biochemical parameters were measured. The Non-HDL-C and TC:HDL-C ratio were also calculated employing their respective formula. Results Body mass index (BMI), waist circumference (WC), blood pressure and lipid parameters were significantly different between diabetic subjects and non-diabetic subjects. There was increased non-HDL-C and TC:HDL-C ratio in subjects with diabetes mellitus. Furthermore, statistically significant correlations of non-HDL-C and TC:HDL-C ratio were obtained with BMI, WC, total cholesterol, HDL-C and LDL-C in diabetic subjects. Conclusions The present study observation revealed that the Non-HDL-C and TC: HDL-C strongly correlate with established independent risk factors such as obesity(WC), elevated blood pressure, HDL-C and LDL-C in diabetes. Thus, the evaluation of Non-HDL-C and TC: HDL-C ratio can be used as the simple, cost-effective and cumulative marker of cardiovascular risk in diabetes mellitus.http://dx.doi.org/10.3126/kumj.v8i4.6239 Kathmandu Univ Med J 2010;8(4):398-404 


2020 ◽  
Author(s):  
Zhijun Wu ◽  
Zhe Huang ◽  
Alice H. Lichtenstein ◽  
Cheng Jin ◽  
Shuohua Chen ◽  
...  

Abstract Background: Experimental studies found that the functionality of high density lipoprotein cholesterol (HDL-C) may be lost in the presence of diabetes mellitus (DM). We prospectively tested whether DM modified the association between HDL-C concentrations and cardiovascular disease (CVD).Methods: Included were 91,354 Chinese adults (8,244 participants with DM and 83,110 participants without DM) without use of lipid-lowering drugs and free of CVD or cancer at baseline (2006). The primary endpoint of interest was a composite of CVD (myocardial infarction, ischemic stroke and hemorrhagic stroke). Cumulative average HDL-C concentrations were calculated from all available HDL-C measures at baseline (2006) and during the follow-up period (2008, 2010, 2012 and 2014).Results: During a mean of 10.4 year of follow-up, there were 5,076 CVD events identified. Presence of DM significantly modified the association between HDL-C concentrations and CVD risk (Pinteraction =0.003). The association between HDL-C concentrations and CVD followed a U-shaped curve in individuals without DM (Pnonlinearity <0.001). The adjusted hazard ratio (HR) of CVD was 1.25 (95% confidence interval (CI): 1.06-1.48) for HDL-C concentrations <1.04 mmol/L and 1.80 (95% CI: 1.56-2.07) for HDL-C concentrations >2.07 mmol/L, relative to the lowest risk group (HDL-C concentrations of 1.30-1.42mmol/L). In participants with DM, higher HDL-C concentrations were associated with a higher risk of CVD, in a dose-response manner (Pnonlinearity =0.44; Ptrend <0.001). The adjusted HR of CVD was 1.63 (95%CI: 1.20-2.20) for HDL-C concentrations >2.07 mmol/L, relative to HDL-C concentrations of 1.30-1.42mmol/L. Conclusion: High HDL-C concentrations were paradoxically associated with increased risk of composite CVD outcomes in individuals with or without DM. However, low HDL-C concentrations failed to predict future CVD risk in individuals with DM.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Susanna Calling ◽  
Sven-Erik Johansson ◽  
Moa Wolff ◽  
Jan Sundquist ◽  
Kristina Sundquist

Abstract Background Identifying variables predictive of acute myocardial infarction (AMI) in women is important. The use of the ratio of total cholesterol-to-high density lipoprotein cholesterol (TC/HDL-C) is often overlooked. The aim was to study TC/HDL-C in relation to later AMI, in a large sample of women, adjusted for age, educational status, smoking, waist-hip ratio, blood pressure, and neighbourhood socioeconomic status. The hypothesis was that increasing TC/HDL-C is associated with an increased risk of later AMI. Methods From December 1995 to February 2000, 6147 women aged 50–59 years from the Womens’ Health in Lund area (WHILA) study in southern Sweden underwent a physical examination, laboratory tests and filled in a questionnaire. The women were followed through national registers for incidence of AMI during a mean follow up of 17 years. Results An increasing TC/HDL-C showed a strong relationship with AMI, with the lowest hazard ratio (HR = 1) in women with a ratio of ≤3.5. The HR for AMI was 1.14 (95% CI: 0.73–1.78) for those with a ratio between 3.5 and 4.0; in those with a ratio between 4.0 and 5.0 the HR for AMI was 1.46 (95% CI: 1.00–2.13) and in those with a ratio > 5.0 the HR was 1.89 (95% CI 1.26–2.82), after adjusting for potential confounding factors. Conclusions TC/HDL-C ratio is a powerful predictor of AMI in middle-aged women. The results indicate that this variable should be used in clinical practice and is important for early identification of individuals at risk of AMI.


2021 ◽  
Vol 18 (1) ◽  
pp. 45-48
Author(s):  
Rabindra Simkhada ◽  
Sanjay Singh KC ◽  
Dharma Nath Yadav ◽  
Ravi Sahi

Background and Aims: Postmenopausal diabetic female are at increased risk of cardiovascular disease. The objective of this study was to study their lipid profile and prevalence of dyslipidemia and assess relation of control of lipid components with various risk factors. Methods: A cross sectional prospective study conducted at Shahid Gangalal National Heart Centre from 15th July 2020 to 14th October 2020 including 109 postmenopausal diabetic female. Detailed history along with clinical examination were conducted. Fasting lipid profile and other relevant investigations were obtained. Results: Mean age of participants was 63.48±9.26 years. Mean age of menopause was 48.59±1.88 years. A total of 37 (33.9%) were hypertensive, 17 (15.6%) were smoker, 67 (61.5%) were physically inactive. A total of 91 (83.5%) were non-vegetarian. Thirty eight (34.9%) had their blood sugar controlled with hemoglobin A1c of <7%. The mean total cholesterol and high density lipoprotein were 5.21±0.97 mmol/l and 1.02±0.13 mmol/l. Similarly mean triglyceride and low density lipoprotein were 2.24±0.75 mmol/l and 3.04±0.12 mmol/l. Dyslipidemia was present in 82.6%. Significant correlation of control of blood sugar with total cholesterol control status (R=0.28, P=0.01), low density lipoprotein control status (R=0.38, P=0.01), high density lipoprotein control status (R=0.36, P=0.04) and triglyceride control status (R=0.30, P=0.04) were seen. Conclusion: Dyslipidemia was common in post menopausal diabetic female. Blood sugar control status showed significant correlation with lipid profile parameters. A good sugar control and evaluation for lipid abnormalities is recommended in postmenopausal diabetic female.


VASA ◽  
2014 ◽  
Vol 43 (3) ◽  
pp. 189-197 ◽  
Author(s):  
Yiqiang Zhan ◽  
Jinming Yu ◽  
Rongjing Ding ◽  
Yihong Sun ◽  
Dayi Hu

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.


2019 ◽  
Vol 3 (8) ◽  
pp. 1503-1517 ◽  
Author(s):  
Alexandra B Kinzer ◽  
Robert D Shamburek ◽  
Marissa Lightbourne ◽  
Ranganath Muniyappa ◽  
Rebecca J Brown

Abstract Context Patients with lipodystrophy have dyslipidemia and insulin resistance. Leptin treatment with metreleptin in lipodystrophy decreases insulin resistance and lowers triglycerides without changing high-density lipoprotein. Detailed measurement of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy can offer insights into cardiovascular disease (CVD) risk and lipid metabolism beyond a standard lipid panel. We hypothesized that patients with lipodystrophy would have a more atherogenic lipid profile than controls at baseline, which would be ameliorated with metreleptin treatment. Objective To characterize the lipoprotein profile in patients with lipodystrophy compared with controls and to evaluate effects of metreleptin treatment. Design, Setting, Patients, and Intervention Patients with lipodystrophy (N = 17) were studied before and after metreleptin for 2 weeks and 6 months and compared with 51 insulin-sensitive sex-matched controls. Main Outcome Measures Lipoprotein profiles were measured by NMR with the LP4 deconvolution algorithm, which reports triglyceride-rich lipoprotein particles (TRLPs), high-density lipoprotein particles (HDLPs), and low-density lipoprotein particles (LDLPs). Results Patients with lipodystrophy had elevated large TRLPs and smaller HDLPs and LDLPs compared with controls. Five patients with lipodystrophy had chylomicrons, compared with zero controls. Metreleptin decreased the size and concentration of TRLPs, eliminated chylomicrons in all but one patient, decreased LDLPs, and increased LDLP size. Metreleptin treatment did not have major effects on HDLPs. Conclusions Patients with lipodystrophy had an atherogenic lipoprotein profile at baseline consistent with elevated CVD risk, which improved after metreleptin treatment. The presence of fasting chylomicrons in a subset of patients with lipodystrophy suggests saturation of chylomicron clearance by lipoprotein lipase.


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