HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition

Objective: The cardioprotective capacity of HDL (high-density lipoprotein) cholesterol postmenopause has been challenged. HDL subclasses, lipid contents, and function might be better predictors of cardiovascular risk than HDL cholesterol. Changes in these measures have not been characterized over the menopause transition (MT) with respect to timing relative to the final menstrual period. Approach and Results: Four hundred seventy-one women with HDL particle (HDL-P) subclasses (nuclear magnetic resonance spectroscopy total, large, medium, and small HDL-P and HDL size), HDL lipid content (HDL phospholipids and triglycerides), and HDL function (cholesterol efflux capacity [HDL-CEC]) measured for a maximum of 5 time points across the MT were included. HDL cholesterol and total HDL-P increased across the MT. Within the 1 to 2 years bracketing the final menstrual period, large HDL-P and HDL size declined while small HDL-P and HDL-triglyceride increased. Although overall HDL-CEC increased across the MT, HDL-CEC per HDL-P declined. Higher concentrations of total, large, and medium HDL-P and greater HDL size were associated with greater HDL-CEC while of small HDL-P were associated with lower HDL-CEC. Associations of large HDL-P and HDL size with HDL-CEC varied significantly across the MT such that higher large HDL-P concentrations and greater HDL size were associated with lower HDL-CEC within the 1 to 2 years around the final menstrual period. Conclusions: Although HDL cholesterol increased over the MT, HDL subclasses and lipid content showed adverse changes. While overall HDL-CEC increased, HDL-CEC per HDL-P declined, consistent with reduced function per particle. Large HDL-P may become less efficient in promoting HDL-CEC during the MT.

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Correction to: HDL (High-Density Lipoprotein) Subclasses, Lipid Content, and Function Trajectories Across the Menopause Transition: SWAN-HDL Study

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atv.0000000000000142 ◽

2021 ◽

Vol 41 (5) ◽

Keyword(s):

High Density Lipoprotein ◽

Lipid Content ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Subclasses ◽

Menopause Transition ◽

And Function

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Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis

Lipids in Health and Disease ◽

10.1186/s12944-019-1170-9 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 2

Author(s):

Tianhua Zhang ◽

Jin Chen ◽

Xiaoyu Tang ◽

Qin Luo ◽

Danyan Xu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Adipose Tissue ◽

Hormone Secretion ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Atherosclerotic Cardiovascular Disease ◽

Nutritional Disorder ◽

Hdl Function ◽

And Function

AbstractObesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.

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

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314050 ◽

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.

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Abstract MP36: Changes in High-density Lipoprotein (hdl) Subclasses and Particle Size Over the Menopause Transition are Associated With Higher Levels of Complement Proteins C3 and C4. The Study of Women's Health Across the Nation Hdl Ancillary Study

Circulation ◽

10.1161/circ.141.suppl_1.mp36 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Samar R El Khoudary ◽

Xirun Chen ◽

Dan McConnell ◽

Maria M Brooks ◽

Trevor Orchard ◽

...

Keyword(s):

Particle Size ◽

High Density Lipoprotein ◽

Piecewise Linear ◽

Density Lipoprotein ◽

Premenopausal Women ◽

High Density ◽

Resonance Spectroscopy ◽

Mixed Effect ◽

Complement Proteins ◽

Menopause Transition

Objective: High density lipoprotein (HDL) is emerging as a key player in modulating inflammation-related response impacting atherosclerosis development. HDL carries multiple proteins with direct roles in complement system activation including C3 and C4. Postmenopausal women have higher levels of C3 than premenopausal women suggesting a role of the menopause transition (MT) in modulating complement proteins. Preliminary work showed significant declines in large HDL particles (HDL-P) and overall HDL particle size, but increases in small HDL-P during the MT. Whether these changes contribute to higher levels of C3 reported after menopause is not known. Our objectives were to test whether C3 and C4 increase around the final menstrual period (FMP) and whether changes in HDL subclasses over the MT associate with C3 and C4 levels in midlife women. Design: We evaluated 558 women (at baseline: age 49.9(2.8) years; 86.6% perimenopausal) who had nuclear magnetic resonance spectroscopy HDL subclasses, C3 and C4 measured up to 5 times over the MT. Piecewise linear mixed-effects models were used to estimate and compare yearly changes in C3 and C4 at 3 time segments relative to the FMP. Linear mixed effect models were used to test associations between changes in each HDL subclass and overall HDL particle size with C3 and C4 separately. Results: Adjusted annual changes in C3 and C4 varied by time segments relative to FMP with significant increases only observed within 1 year before to 2 years after the FMP ( Figure ). These changes were significantly greater than changes in the other 2 time segments. Greater decreases in large and increases in small HDL-P concentrations and decreases in the overall size of HDL-P were independently associated with higher levels of C3 and C4 over time ( Table ). Conclusions: Complement proteins C3 and C4 significantly rise around menopause with C3 showing the steepest rise. Changes in HDL subclasses and overall size over the MT may play role in modulating inflammation responses known to be related to atherosclerosis.

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Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function

International Journal of Molecular Sciences ◽

10.3390/ijms21238985 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8985

Author(s):

Julia T. Stadler ◽

Gunther Marsche

Keyword(s):

High Density Lipoprotein ◽

Virgin Olive Oil ◽

Lipoprotein Metabolism ◽

Density Lipoprotein ◽

High Density ◽

Atherogenic Dyslipidemia ◽

Hdl Function ◽

Increased Risk ◽

And Function ◽

The Impact

In obese individuals, atherogenic dyslipidemia is a very common and important factor in the increased risk of cardiovascular disease. Adiposity-associated dyslipidemia is characterized by low high-density lipoprotein cholesterol (HDL-C) levels and an increase in triglyceride-rich lipoproteins. Several factors and mechanisms are involved in lowering HDL-C levels in the obese state and HDL quantity and quality is closely related to adiponectin levels and the bioactive lipid sphingosine-1-phosphate. Recent studies have shown that obesity profoundly alters HDL metabolism, resulting in altered HDL subclass distribution, composition, and function. Importantly, weight loss through gastric bypass surgery and Mediterranean diet, especially when enriched with virgin olive oil, is associated with increased HDL-C levels and significantly improved metrics of HDL function. A thorough understanding of the underlying mechanisms is crucial for a better understanding of the impact of obesity on lipoprotein metabolism and for the development of appropriate therapeutic approaches. The objective of this review article was to summarize the newly identified changes in the metabolism, composition, and function of HDL in obesity and to discuss possible pathophysiological consequences.

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How Do We Approach Low High-density Lipoprotein Cholesterol in 2011?

European Cardiology Review ◽

10.15420/ecr.2011.7.4.257 ◽

2011 ◽

Vol 7 (4) ◽

pp. 257

Author(s):

Esther Godfrey ◽

Julian PJ Halcox ◽

◽

Keyword(s):

Clinical Practice ◽

High Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Cvd Risk ◽

Risk Assessment Models ◽

The Metabolic Syndrome ◽

Hdl Function ◽

Atherogenic Dyslipidaemia

The prevalence of obesity and of the metabolic syndrome is increasing worldwide, and the management of global cardiovascular disease (CVD) risk requires strategies for the treatment of complex, pro-atherogenic dyslipidaemia. Considerable evidence provides a scientific rationale for the role of high-density lipoprotein (HDL) in atheroprotection. Although HDL function can become altered in pathological states, the quantitative evaluation of HDL cholesterol (HDL-C) in addition to total cholesterol (TC) levels improves the accuracy of CVD risk prediction, and is therefore a component of most global CVD risk assessment models. Non-pharmacological lifestyle interventions, such as diet and exercise for weight loss and smoking cessation, are the mainstay of raising HDL in clinical practice. Several HDL-raising medications are available but, beyond statin therapy, evidence of an incremental clinical benefit is limited. Potent novel HDL therapeutics are emerging that not only increase HDL-C levels but may also improve HDL function. Early data have restored some confidence in the potential of new cholesteryl ester transfer protein (CETP) antagonists in clinical practice. It is essential that clinical trials address vascular burden and patient outcomes, and data from large outcome trials are eagerly awaited.

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High-Density Lipoprotein (HDL) in Allergy and Skin Diseases: Focus on Immunomodulating Functions

Biomedicines ◽

10.3390/biomedicines8120558 ◽

2020 ◽

Vol 8 (12) ◽

pp. 558

Author(s):

Athina Trakaki ◽

Gunther Marsche

Keyword(s):

High Density Lipoprotein ◽

Skin Diseases ◽

Immune Cell ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Cholesterol Levels ◽

Lipid Transporters ◽

Composition Structure ◽

And Function

From an evolutionary perspective, lipoproteins are not only lipid transporters, but they also have important functions in many aspects of immunity. High-density lipoprotein (HDL) particles are the most abundant lipoproteins and the most heterogeneous in terms of their composition, structure, and biological functions. Despite strong evidence that HDL potently influences the activity of several immune cells, the role of HDL in allergies and skin diseases is poorly understood. Alterations in HDL-cholesterol levels have been observed in allergic asthma, allergic rhinitis, atopic dermatitis (eczema), psoriasis, urticaria, and angioedema. HDL-associated apolipoprotein (apo) A-I, apoA-IV, and apoC-III, and lyso-phosphatidylcholines potently suppress immune cell effector responses. Interestingly, recent studies provided evidence that allergies and skin diseases significantly affect HDL composition, metabolism, and function, which, in turn, could have a significant impact on disease progression, but may also affect the risk of cardiovascular disease and infections. Interestingly, not only a loss in function, but also, sometimes, a gain in function of certain HDL properties is observed. The objective of this review article is to summarize the newly identified changes in the metabolism, composition, and function of HDL in allergies and skin diseases. We aim to highlight the possible pathophysiological consequences with a focus on HDL-mediated immunomodulatory activities.

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Abstract P101: Premenopausal Life’s Simple 7 Score Is Associated With High-density Lipoprotein Metrics Later In Life: The SWAN HDL Study

Circulation ◽

10.1161/circ.143.suppl_1.p101 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Alexis Nasr ◽

Karen A Matthews ◽

Maria M Brooks ◽

Trevor Orchard ◽

Dan McConnell ◽

...

Keyword(s):

High Density Lipoprotein ◽

Cardiovascular Health ◽

Menopausal Status ◽

Density Lipoprotein ◽

High Sensitivity ◽

High Density ◽

Resonance Spectroscopy ◽

Hdl Function ◽

Life’S Simple 7 ◽

Life's Simple 7

Objective: In midlife women, higher high-density lipoprotein cholesterol (HDL-C) is not always associated with cardio-protection, suggesting a potential dysfunction of HDL. Novel metrics of HDL may provide further information on its cardio-protective features. The AHA developed the Life’s Simple 7 (LS7) score based on 7 lifestyle factors (cholesterol, BMI, diet, physical activity, smoking, glucose and blood pressure). A higher LS7 indicates a healthier lifestyle and is to cardiovascular health. We aimed to assess if higher premenopausal LS7 score is associated with a protective future HDL metrics profile as measured by greater HDL function (cholesterol efflux capacity), lower HDL-triglycerides (HDL-Tg) and higher HDL-phospholipids (HDL-PL) contents, higher large HDL-particles (HDL-P) and lower small HDL-P levels and larger overall HDL size by nuclear magnetic resonance spectroscopy. Methods: We included 529 women [baseline age 46.4 (2.6) years, 57% (299 of 529) White] from the Study of Women’s Health Across the Nation (SWAN) HDL ancillary study who had premenopausal LS7 score followed by repeated HDL metrics at later visits [time between LS7 score and first HDL measure: 3.9 (1.4) years]. Multivariable linear mixed models were used to analyze the independent association between premenopausal LS7 score and each HDL metric. Results: After adjusting for race, education, and baseline age, menopausal status, economic hardship and high-sensitivity C-reactive protein (Table), higher premenopausal LS7 score was associated with lower HDL-Tg (p<0.0001) and higher HDL-PL (p=0.02), greater total HDL-P (p=0.03), large HDL-P (p=0.0001) and HDL-C (p<0.0001), and larger HDL size (p<0.0001) later in life. Premenopausal LS7 score was not related to HDL function. Conclusion: Higher premenopausal LS7 score was not related to HDL function but related to favorable future HDL contents and subclasses. This indicates that a better premenopausal lifestyle and metabolic health may contribute to a better HDL profile later in life.

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High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Cells ◽

10.3390/cells10030574 ◽

2021 ◽

Vol 10 (3) ◽

pp. 574

Author(s):

Maria Pia Adorni ◽

Nicoletta Ronda ◽

Franco Bernini ◽

Francesca Zimetti

Keyword(s):

High Density Lipoprotein ◽

Cholesterol Efflux ◽

Current Knowledge ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Current Evidence ◽

Endocrine Disorders ◽

Lifestyle Modifications ◽

Cholesterol Efflux Capacity

Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. The present review describes the current knowledge on HDL CEC modifications in these conditions, focusing on the most recent human studies and on genetic and pathophysiologic aspects. In addition, the most relevant strategies possibly modulating HDL CEC, including lifestyle modifications, as well as nutraceutical and pharmacological interventions, will be discussed. The objective of this review is to help understanding whether, from the current evidence, HDL CEC may be considered as a valid biomarker of CV risk and a potential pharmacological target for novel therapeutic approaches.

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