scholarly journals Serum modified HDL was associated with cardiovascular disease in a Japanese community-based cohort

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
T Okamura ◽  
M Sata ◽  
M Iida ◽  
A Kakino ◽  
S Harada ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Predictive Marker ◽  
High Density ◽  
Apolipoprotein A1 ◽  
Lipid Lowering ◽  
Increased Risk

Abstract Background Previous studies have shown that high density lipoprotein (HDL) is protective against cardiovascular disease (CVD). However, recent studies suggested that function of HDL was more important than HDL cholesterol levels. The present study aimed to clarify the relationship between modified HDL levels and CVD incidence. Methods LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates modified LDL (low density lipoprotein) activity; however, some lipoproteins with apolipoprotein A1 (Apo A-1) are also bonded to LOX-1. In this study, serum LOX-1 ligand containing Apo A-1 was defined as modified HDL, which were measured by our new development method. We conducted a nested case-control study in a Japanese cohort study, involving 11,002 community dwellers. During 4.0 years follow-up, we observed 127 new CVD onsets. For each CVD case, age and sex matched three controls were randomly selected (N = 381). Serum samples collected at baseline survey stored at − 80 °C were used for the measurement of modified HDL. We estimated multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between modified HDL levels and CVD by conditional logistic regression. Results Modified HDL levels were associated with increased risk of CVD (OR for one unit increase of log transformed modified HDL, 2.05: 95% CI, 1.16-3.62) after adjustment for body mass index, hypertension, diabetes, LDL cholesterol, HDL cholesterol, lipid lowering agents, chronic kidney disease, smoking and alcohol drinking. The magnitude of OR was almost equivalent to those of hypertension and diabetes, which were 2.33 (95% CI, 1.37-3.98) and 2.61 (95% CI, 1.48-4.59), respectively. On the other hands, other lipids markers showed relatively weak associations with CVD. Conclusions Serum modified HDL, i.e., LOX-1 ligand containing Apo A-1, might be a novel predictive marker for CVD in apparently healthy individuals. Key messages Recent epidemiologic studies suggested that function of high-density lipoprotein (HDL) was more important than HDL cholesterol level itself to predict cardiovascular disease. Modified HDL measured by a novel cell-free, non-fluorescent method as LOX-1 ligand containing Apo A-1, was a predictive marker for CVD after adjusting for other traditional risk factors.

Abstract 13272: High Density Lipoprotein Subclasses Predict Non-Cardiovascular Disease, Non-Cancer Chronic Inflammatory-Related Death and Hospitalization More Strongly than Cardiovascular Disease Events in the Multi-Ethnic Study of Atherosclerosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Daniel Duprez ◽  
James Otvos ◽  
Kenneth Feingold ◽  
Philip Greenland ◽  
Myron D Gross ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Inflammatory Markers ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipid Lowering ◽  
Ethnic Study ◽  
Lipoprotein Particles ◽  
D Dimer

In vitro studies have demonstrated that high density lipoprotein particles (HDL-P) antagonize inflammatory processes. We studied the predictive value of HDL-P and inflammatory markers for incident cardiovascular disease (CVD) and non-CVD, non-cancer, chronic inflammatory-related events. Methods: In the Multi-Ethnic Study of Atherosclerosis, we studied 6475 men and women free of overt CVD, baseline age 45-84 years, who had fasting venous samples for lipid profile, lipoprotein particles, and inflammatory markers Interleukin-6 (IL-6), hs-CRP and D-dimer at baseline. Median follow-up was 10.1 years. Poisson regression models predicted non-CVD, non-cancer, chronic inflammatory-related events (death and hospitalization), based on diagnostic codes, n=1054) and CVD events due to coronary heart disease, myocardial infarction, coronary artery disease requiring revascularization, stroke, peripheral arterial disease, congestive heart failure and CVD or unwitnessed death (adjudicated, n=756). Adjustment was for age, race, gender, clinic, heart rate, smoking, body mass index, blood pressure, blood pressure and lipid lowering medication, diabetes mellitus, plus all lipid, lipoprotein particle and inflammatory variables. Results: Non-CVD, non-cancer, chronic inflammatory-related events were inversely associated with the sum of small+medium HDL-P independent of covariates (relative risk (RR) per standard deviation (95% confidence limits), RR: 0.85 (0.79-0.91, P < 0.0001). Non-CVD, non-cancer, chronic inflammatory-related events were positively associated with IL-6, RR:1.19 (1.11-1.27, P < 0.0001) and D-dimer, RR: 1.10 (1.05-1.16, P < 0.0001). CVD was associated with small+medium HDL-P, RR: 0.90 (0.82-0.99, P < 0.03) and IL-6, RR:1.15 (1.06-1.25 P < 0.0001). hsCRP was unrelated to either outcome after adjustment for other inflammatory markers. Conclusion: The long-term inverse association of small+medium HDL-P with non-CVD, non-cancer, chronic inflammatory-related death and hospitalization was stronger than with fatal and non-fatal CVD in subjects initially free of overt CVD. These findings provide clinical evidence that small+medium HDL-P have anti-inflammatory properties and may rethink the importance of HDL-P beyond CVD.

The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis

2021 ◽  
Vol 28 ◽  
Author(s):  
Shiva Ganjali ◽  
Gerald F. Watts ◽  
Maciej Banach ◽  
Željko Reiner ◽  
Petr Nachtigal ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Association Studies ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
Genome Wide Association Studies ◽  
Increased Risk

Abstract: The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non-ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.

scholarly journals High-Density Lipoprotein (HDL) Triglyceride and Oxidized HDL: New Lipid Biomarkers of Lipoprotein-Related Atherosclerotic Cardiovascular Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 362 ◽  
Author(s):  
Fumiaki Ito ◽  
Tomoyuki Ito
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxide ◽  
Hdl Cholesterol ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Panel ◽  
Lipid Markers ◽  
Dysfunctional Hdl

Lipid markers are well-established predictors of vascular disease. The most frequently measured lipid markers are total cholesterol, high-density lipoprotein (HDL)-cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglyceride. HDL reduces atherosclerosis by multiple mechanisms, leading to a reduced risk of cardiovascular disease, and HDL-C, as a metric of HDL quantity, is inversely associated with cardiovascular disease, independent of LDL-C. However, the quality of the HDL appears to be more important than its quantity, because HDL loses its antiatherogenic functions due to changes in its composition and becomes “dysfunctional HDL”. Although there is evidence of the existence of “dysfunctional HDL”, biomarkers for monitoring dysfunctional HDL in clinical practice have not yet been established. In this review, we propose a new lipid panel for the assessment of dysfunctional HDL and lipoprotein-related atherosclerotic cardiovascular disease. The lipid panel includes the measurement of lipid peroxide and triglyceride contents within HDL particles.

scholarly journals Patterns and trends of potentially inappropriate high-density lipoprotein cholesterol testing in Australian adults at high risk of cardiovascular disease from 2008 to 2014: analysis of linked individual patient data from the Australian Medicare Benefits Schedule and Pharmaceutical Benefits Scheme

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e019041 ◽  
Author(s):  
Farshid Hajati ◽  
Evan Atlantis ◽  
Katy J L Bell ◽  
Federico Girosi
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
National Guidelines ◽  
Pharmaceutical Benefits Scheme

ObjectivesWe examine the extent to which the adult Australian population on lipid-lowering medications receives the level of high-density lipoprotein cholesterol (HDL-C) testing recommended by national guidelines.DataWe analysed records from 7 years (2008–2014) of the 10% publicly available sample of deidentified, individual level, linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) electronic databases of Australia.MethodsThe PBS data were used to identify individuals on stable prescriptions of lipid-lowering treatment. The MBS data were used to estimate the annual frequency of HDL-C testing. We developed a methodology to address the issue of ‘episode coning’ in the MBS data, which causes an undercounting of pathology tests. We used a published figure on the proportion of unreported HDL-C tests to correct for the undercounting and estimate the probability that an HDL-C test was performed. We judged appropriateness of testing frequency by comparing the HDL-C testing rate to guidelines’ recommendations of annual testing for people at high risk for cardiovascular disease.ResultsWe estimated that approximately 49% of the population on stable lipid-lowering treatment did not receive any HDL-C test in a given year. We also found that approximately 19% of the same population received two or more HDL-C tests within the year. These levels of underutilisation and overutilisation have been changing at an average rate of 2% and −4% a year, respectively, since 2009. The yearly expenditure associated with test overutilisation was approximately $A4.3 million during the study period, while the cost averted because of test underutilisation was approximately $A11.3 million a year.ConclusionsWe found that approximately half of Australians on stable lipid-lowering treatment may be having fewer HDL-C testing than recommended by national guidelines, while nearly one-fifth are having more tests than recommended.

scholarly journals Novel Insights From Human Studies on the Role of High-Density Lipoprotein in Mortality and Noncardiovascular Disease

2020 ◽  
Author(s):  
Christian M. Madsen ◽  
Anette Varbo ◽  
Børge G. Nordestgaard
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Therapeutic Potential ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Cancer Type ◽  
Health And Disease ◽  
And Function

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic, studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.

scholarly journals CORRELATION OF SERUM HIGH-DENSITY LIPOPROTEIN CHOLESTEROL AND HOMOCYSTEINE LEVEL IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

2019 ◽  
Vol 25 (1) ◽  
pp. 99
Author(s):  
Yayie Dwina Putri ◽  
Tuty Prihandani ◽  
Lillah Lillah ◽  
Rismawati Yaswir
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Acute Myocardial Infarction ◽  
High Density Lipoprotein ◽  
Homocysteine Level ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
The Mean ◽  
Spearman’S Correlation

Acute Myocardial Infarction (AMI), one of the primary manifestation of coronary heart disease, is a significat cause of death worldwide. Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional or genetic disturbances in homocysteine metabolism. The role of hyperhomocysteinemia in altered lipid metabolism presumed holds the key to an increased risk of cardiovascular disease. Hyperhomocysteinemia causes the reduction of serum High-Density Lipoprotein (HDL) cholesterol level by inhibiting hepatic synthesis of apo-A1 (significant apolipoprotein HDL). The aim of this study was to know the correlation between hyperhomocysteinemia and decreased HDL cholesterol levels for the management of cardiovascular disease risk factors. This research was an analytical study with cross-sectional design in 40 patients AMI who meet the inclusion and exclusion criteria and conduct blood test at the Central Laboratory of Hospital Dr. M. Djamil Padang and Biomedical Laboratory Faculty of Medicine Andalas University. The study was conducted in May 2016-Agustus 2017. Homocysteine level was measured by ELISA method. High-Density Lipoprotein level was performed by enzymatic colorimetric method. Data were analyzed by Spearman’s correlation test. Research subjects were 40 people with male gender 30 (75%) and female 10 (25%), mean age 61.08 (11.09) year. The mean level of HDL cholesterol in patients with AMI is 41.93 ± 13.12 mg/dL. The mean level of homocysteine in patients with AMI is 25.36 ± 22.2 µmol/L. Spearman’s correlation test showed a strong correlation between the levels of homocysteine and HDL cholesterol with r=-0.603 and p<0.01.

scholarly journals Roles of Reconstituted High-Density Lipoprotein Nanoparticles in Cardiovascular Disease: A New Paradigm for Drug Discovery

2020 ◽  
Vol 21 (3) ◽  
pp. 739 ◽  
Author(s):  
Jiansheng Huang ◽  
Dongdong Wang ◽  
Li-Hao Huang ◽  
Hui Huang
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Inverse Correlation ◽  
Hdl Cholesterol ◽  
High Density ◽  
Atherosclerotic Cardiovascular Disease ◽  
New Paradigm

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear.

Non-high-density-lipoprotein cholesterol and cardiovascular risk factors among adolescents with and without impaired fasting glucose

2009 ◽  
Vol 34 (2) ◽  
pp. 136-142 ◽  
Author(s):  
Jian Liu ◽  
Divya Joshi ◽  
Christopher T. Sempos
Keyword(s):  
High Density Lipoprotein ◽  
Impaired Fasting Glucose ◽  
Fasting Glucose ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Important Indicator ◽  
Increased Risk

To evaluate how non-high-density-lipoprotein (non-HDL) is associated with impaired fasting glucose (IFG) and clustered metabolic risk (MR) factors among adolescents, we pooled 2764 adolescents, aged 12–19 years, from the National Health and Nutrition Examination Survey from 3 time periods (1999–2000, 2001–2002, and 2003–2004) who were free of diabetes and had fasted overnight for this analysis. IFG was defined as 100 ≤ glucose ≤ 125 mg·dL–1. Age- and sex-specific cut-offs were used for 4 MR factors: higher levels of triglycerides, waist circumference, blood pressure, and lower levels of HDL. Clustered MR was defined as having any 2 of the 4 factors. Overall, approximately 11% of adolescents had IFG. The mean level of non-HDL cholesterol was much higher in those with IFG than in those without IFG, with adjustment for certain confounding variables (121.4 vs. 110.1 mg·dL–1; p < 0.05). This difference could still be observed in adolescents with one or more clustered MR factors. However, there were no statistical differences in low-density-lipoprotein (LDL) level. Compared with those who were without IFG and not at high levels of non-HDL — after adjustment for age, sex, race, current smoking, and body mass index — the odds of having clustered MR factors were 1.08 (95% CI, 0.65–1.82) for those with IFG and low non-HDL cholesterol, 3.55 (2.29–5.48) for those without IFG but with high non-HDL cholesterol, and 10.10 (3.67–27.80) for those with both IFG and high non-HDL cholesterol. Moreover, those with IFG and at increased risk of obesity were more likely to have higher levels of non-HDL cholesterol (odds ratio (95% CI): 4.41 (2.28–8.50)), compared with those without IFG and not at increased risk of obesity. In summary, prediabetic adolescents with IFG and high levels of non-HDL cholesterol are more likely to have clustered MR factors. Thus, the levels of non-HDL cholesterol may be an important indicator in monitoring cardiovascular disease risk among adolescents with IFG.

scholarly journals Subpopulations of High-Density Lipoprotein: Friends or Foes in Cardiovascular Disease Risk in Chronic Kidney Disease?

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 554
Author(s):  
Susana Coimbra ◽  
Flávio Reis ◽  
Maria João Valente ◽  
Susana Rocha ◽  
Cristina Catarino ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Density Lipoprotein ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Size Composition ◽  
High Density

Dyslipidemia is a major traditional risk factor for cardiovascular disease (CVD) in chronic kidney disease (CKD) patients, although the altered lipid profile does not explain the number and severity of CVD events. High-density lipoprotein (HDL) is a heterogeneous (size, composition, and functionality) population of particles with different atherogenic or atheroprotective properties. HDL-cholesterol concentrations per se may not entirely reflect a beneficial or a risk profile for CVD. Large HDL in CKD patients may have a unique proteome and lipid composition, impairing their cholesterol efflux capacity. This lack of HDL functionality may contribute to the paradoxical coexistence of increased large HDL and enhanced risk for CVD events. Moreover, CKD is associated with inflammation, oxidative stress, diabetes, and/or hypertension that are able to interfere with the anti-inflammatory, antioxidative, and antithrombotic properties of HDL subpopulations. How these changes interfere with HDL functions in CKD is still poorly understood. Further studies are warranted to fully clarify if different HDL subpopulations present different functionalities and/or atheroprotective effects. To achieve this goal, the standardization of techniques would be valuable.

scholarly journals Different Associations between High Density Lipoprotein Cholesterol and Cardiovascular Diseases in Diabetic and Non-diabetic People: A Prospective Community-based Study

2020 ◽  
Author(s):  
Zhijun Wu ◽  
Zhe Huang ◽  
Alice H. Lichtenstein ◽  
Cheng Jin ◽  
Shuohua Chen ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Experimental Studies ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Cvd Risk ◽  
Increased Risk

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.

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