Not All HDL Cholesterol is Good – Size Matters

MedicalResearch.com Interview with:

Samar R. El Khoudary, PhD, MPH, BPharm, FAHA Associate Professor, Epidemiology PITT Public Health Epidemiology Data Center University of Pittsburgh Pittsburgh, PA 15260 

Dr. El Khoudary

Samar R. El Khoudary, Ph.D., M.P.H. BPharm, FAHA
Associate Professor
Department of Epidemiology
University of Pittsburgh Graduate School of Public Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is based on the current measurements used to determine cardiovascular disease risk in postmenopausal women. Higher levels of HDL “good cholesterol” as measured by the widely available clinical test, HDL-Cholesterol, may not always be indicative of a lower risk of cardiovascular disease in postmenopausal women.

HDL is a family of particles found in the blood that vary in sizes, cholesterol contents and function. HDL particles can become dysfunctional under certain conditions such as chronic inflammation. HDL has traditionally been measured as the total cholesterol carried by the HDL particles, known as HDL cholesterol. HDL cholesterol, however, does not necessarily reflect the overall concentration, the uneven distribution, or the content and function of HDL particles.

We looked at 1,138 women aged 45 through 84 enrolled across the U.S. in the Multi-Ethnic Study of Atherosclerosis (MESA), a medical research study sponsored by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). MESA began in 1999 and is still following participants today. We assessed two specific measurements of HDL: the number and size of the HDL particles and total cholesterol carried by HDL particles. Our study also looked at how age when women transitioned into post menopause, and the amount of time since transitioning, may impact the expected cardio-protective associations of HDL measures.

Our study points out that the traditional measure of the good cholesterol, HDL cholesterol, fails to portray an accurate depiction of heart disease risk for postmenopausal women. We reported a harmful association between higher HDL cholesterol and atherosclerosis risk that was most evident in women with older age at menopause and who were greater than, or equal to, 10 years into post menopause. In contrast to HDL cholesterol, a higher concentration of total HDL particles was associated with lower risk of atherosclerosis. Additionally, having a high number of small HDL particles was found beneficial for postmenopausal women. These findings persist irrespective of age and how long it has been since women became postmenopausal.

On the other hand, large HDL particles are linked to an increased risk of cardiovascular disease close to menopause. Women are subject to a variety of physiological changes in their sex hormones, lipids, body fat deposition and vascular health as they transition through menopause. We are hypothesizing that the decrease of estrogen, a cardio-protective sex hormone, along with other metabolic changes, can trigger chronic inflammation over time, which may alter the quality of HDL particles. Future studies should test this hypothesis.

The study findings indicate that measuring size and number of HDL particles can better reflect the well-known cardio-protective features of the good cholesterol in postmenopausal women. Continue reading

Very High ‘Good Cholesterol’ HDL Linked To Increased Risk of Infections

MedicalResearch.com Interview with:

Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital, Denmark

Prof. Nordestgaard

Børge G. Nordestgaard, MD, DMSc
Professor, University of Copenhagen
Chief Physician, Dept. Clinical Biochemistry
Herlev and Gentofte Hospital
Copenhagen University Hospital, Denmark 

MedicalResearch.com: What is the background for this study?

Response: For decades research into the role and function of high-density lipoprotein (HDL) has revolved around the believe that HDL protects against atherosclerotic cardiovascular disease. However, results from large genetic studies and from large randomized clinical trials with HDL cholesterol elevating drugs have all indicated that there is no causal association between HDL cholesterol and risk of atherosclerotic cardiovascular disease.

Given the hitherto strong focus on cardiovascular disease, little is known about the possible role of HDL in other aspects of human health and disease. Preclinical evidence has indicated that HDL might be of importance for normal function of the immune system and susceptibility to infectious disease, but it had never previously been investigated if levels of HDL cholesterol is associated with the risk of infectious disease in individuals from the general population. In the present study we tested this hypothesis in more than 100.000 Danes from the population at large.

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Cholesterol Uptake Capacity, a New Indicator of HDL Functionality, for Cardiovascular Risk Stratification in the Real World.

MedicalResearch.com Interview with:
Amane Harada, PhD
Senior Researcher
Central Research Laboratories, Sysmex Corporation
Kobe, Japan

Ryuji Toh, MD, PhD Associate Professor Division of Evidence-based Laboratory Medicine Kobe University Graduate School of MedicineRyuji Toh, MD, PhD
Associate Professor
Division of Evidence-based Laboratory Medicine
Kobe University Graduate School of Medicine
Kobe, Japan 


MedicalResearch.com: What is the background for this study?

Response: High-density lipoprotein (HDL) exhibits a variety of anti-atherogenic functions including anti-inflammatory and anti-oxidative functions as well as promoting reverse cholesterol transport. However, it has been reported that HDL may lose its anti-atherogenic properties and become “dysfunctional” HDL under pathological conditions.

Recent studies have demonstrated that cholesterol efflux capacity of HDL is a better predictor of CVD than HDL-C, suggesting that not only the quantity, but also the quality of HDL may significantly modulate and predict the progression of cardiovascular disease.

However, the conventional procedure for efflux capacity assay requires radiolabeling and cells, and the procedures are time consuming. Therefore, its clinical application is impractical.

To solve those problems, we have recently developed a new assay system to evaluate the capacity of HDL to accept cholesterol, named “uptake capacity”.

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Test Helps Determine Which Patients May Not Benefit From Elevated HDL

Thomas Weichhart, PhD Associate Professor, Medical University of Vienna Institute of Medical Genetics Vienna AustriaMedicalResearch.com Interview with:
Thomas Weichhart, PhD

Associate Professor, Medical University of Vienna
Institute of Medical Genetics Vienna Austria

Medical Research: What is the background for this study?

Dr.  Weichhart: Impairment of high-density lipoprotein (HDL) function has been associated with cardiovascular events in patients with kidney failure on hemodialysis. The protein composition of HDLs is altered in these patients presumably compromising the cardioprotective effects of HDLs. In an earlier study we found that two proteins in particular, namely Serum Amyloid A (SAA) and Surfactant Protein B (SP-B), are significantly raised in the HDL of dialysis patients, and these also contribute towards HDL losing its protective effect. In the current study we have now developed an novel test that can quickly and directly measure the SAA and SP-B bound to HDL.

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Living To Extreme Old Age Influenced By Genetics, HDL Cholesterol

Sofiya Milman, M.D. Assistant Professor of Medicine Divisions of Endocrinology and Geriatrics Albert Einstein College of MedicineMedicalResearch.com Interview with:
Sofiya Milman, M.D.
Assistant Professor of Medicine
Divisions of Endocrinology and Geriatrics
Albert Einstein College of Medicine

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Milman: Aging is a major risk factor for many diseases, including cardiovascular disease, dementia, and diabetes. Yet, individuals with exceptional longevity delay the onset of most diseases and often escape from age-related illnesses altogether. Exceptional longevity is an inherited trait. A unique cholesterol profile has been previously associated with longevity and specific genetic variations. This profile included elevated levels of high-density lipoprotein (HDL) cholesterol or “good” cholesterol and large HDL particles. The present study explored whether elevated HDL cholesterol levels and genes that control HDL cholesterol can predict survival in individuals age 95 years or older.

The study found that higher levels of HDL cholesterol were related to longer survival in women, but not in men. Higher HDL cholesterol level was also seen in individuals without cognitive problems and diabetes. On the other hand, both men and women with larger HDL particle size and higher levels of APOA1, a protein component of HDL cholesterol, exhibited longer survival. Variants in two genes, the CETP and APOA1, were related to higher HDL cholesterol levels.

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Fenofibrate Improves Cholesterol Profile in Diabetes

MedicalResearch.com Interview with:
Prof. Michael d’Emden
Endocrine Research Unit
Royal Brisbane Hospital, Brisbane, Australia

Medical Research: What are the main findings of the study?

Prof. d’Emden: Our study is the largest trial of women having type 2 diabetes assessing the role of a fibric acid derivative, in this case fenofibrate, ever conducted.  There were 3657 female subjects randomized to placebo or fenofibrate.  The study demonstrated greater reductions in women of total cholesterol, triglycerides and LDL-cholesterol and greater increases in HDL-cholesterol.  In women, fenofibrate decreased total cardiovascular end-points by 30% compared with only 13% in men, although there was no-treatment-by-sex interaction.  The majority of end points assessed revealed a consistent trend to increased benefit being seen in women.

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HDL Function: Improved with Strength Training, Even in Overweight

MedicalResearch.com Interview with:
Christian K. Roberts
Exercise and Metabolic Disease Research Laboratory,
Translational Sciences Section, School of Nursing
University of California, Los Angeles, CA

MedicalResearch.com: How would you best summarize the main findings/results of this study?

Answer: Our main finding was that HDL functioned better in its antioxidant role in subjects who participated in resistance exercise training (i.e. weight training) a minimum of 4 days a week, regardless of their weight—one group was lean (BMI <25) and the other overweight/obese (BMI >27) —than those who didn’t exercise (overweight, BMI >27, and untrained). In addition, HDL had similar effectiveness as an antioxidant in the overweight-trained group as in the as lean-trained group. Although indices of weight were associated with dysfunctional HDL, differences in fitness may be a better measure of who has healthier functioning HDL.

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