Tag Archives: HDL

New Advances In Lipid Genetics Lead To Better Detection And Prevention Of Diabetes, Heart Disease

By identifying those at risk at the earliest stage would mean giving individuals plenty of time to make the lifestyle changes that could help them avoid the disease

RESEARCHERS from the US and The Netherlands have found ways to earlier and better prediction of diseases such as diabetes, atherosclerosis, and heart disease through studying the genetic make-up of different varieties of lipids in blood plasma.

Studying the genetic make-up of different varieties of lipids (fatty molecules) in the blood plasma of an individual can lead to a better and earlier prediction of diseases such as diabetes, atherosclerosis, and heart disease, two researchers reported on Monday at the annual conference of the European Society of Human Genetics, currently in session in Amsterdam, The Netherlands.

In the first study, Dr. Joanne Curran from the Texas Biomedical Research Institute, San Antonio, USA, reported that lipidomic profiling would become a more reliable early indicator of individuals likely to develop diabetes than the more commonly used predictors such as blood glucose and insulin levels.

Dr. Curran and colleagues from the US and Australia measured 356 different lipid varieties from about 1100 Mexican American members of large extended families who were part of the San Antonio Family Heart Study. The Mexican American population is at high risk of diabetes with about 25% of this population ultimately becoming diabetic. At the start of the research, 861 of the individuals studied did not have diabetes. However, over the 10 year follow-up examined in the study, 110 individuals did develop the disease.

The scientists were able to isolate 128 different varieties of lipids that predicted the progression to diabetes by measuring the lipidomic profiles of each individual at multiple timepoints during the follow-up period. “The single best predictor we found was a novel component called dihydroceramide (dhCer). This was substantially increased in people with diabetes. It is also heritable, and appears to be an independent risk factor unconnected to blood sugar and insulin levels,” said Dr. Curran.

After uncovering the link between dhCer and diabetes, the team searched the genome to find locations that harbored genes that influence dhCer levels. They identified a region on chromosome 3 that appeared to contain a gene with substantial importance for the production of dhCer. “Through whole genome sequencing, we are now attempting to identify this causal gene in the hope that it will be informative in the understanding of the pathogenesis of diabetes, and also suggest new avenues for treatment,” Dr. Curran said.

Dr Joanne E. Curran

In the future, the researchers say, measurement of dhCer levels could become routine in the prediction of individuals likely to become diabetic. One of the difficulties of the current predictive methods is that they do not function until a patient is near to developing the disease. Being able to identify those at risk at the earliest stage would mean that individuals have plenty of time to make the lifestyle changes that could help them avoid the disease – through a change in diet, or increasing physical activity, for example.

“Currently one in ten US adults suffers from diabetes and recently the Centers for Disease Control has predicted that this will increase to one in three by 2050,” said Dr. Curran. “We are optimistic that our discovery will lead to new treatments, but in the short-term the importance of finding out at an early stage whether any individual is likely to develop it cannot be overstated. A test based on dhCer levels will help to avoid the serious health effects that diabetes has in its own right, such as kidney failure, amputations, and blindness. It is, of course, also a risk for cardiovascular disease, so the health burden of this condition is enormous”, she was quoted saying in a press release.

In the second study, Dr. Sarah Willems, from the Erasmus Medical Centre, Rotterdam, The Netherlands, described to the conference research carried out on the influence of common genetic lipid variants on atherosclerosis and related heart disease. “A recent genome-wide meta-analysis of more than 100,000 individuals identified a large number of genetic variants associated with levels of LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. These molecules are, at increased levels of LDL and triglycerides and decreased levels of HDL, important risk factors for cardiovascular disease”, said Dr. Willems.

Dr Sarah Willems

“As our knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events,” Willems’ group told attendees.

The researchers used risk scores from these genetic variants to test the hypothesis that their cumulative effects were associated with cardiovascular disease. For this purpose they used genetic data from more than 8000 individuals from the population-based Rotterdam Study and more than 2000 individuals participating in the Dutch family-based Erasmus Rucphen Family study.

They found an association between the LDL risk score and arterial wall thickness, and a strong association of this risk score with carotid plaque. These conditions can cause arterial blockage which leads to stroke. The same risk score was also associated with coronary heart disease.

“Our findings show that an accumulation of common genetic variants with small effects on lipid levels can have a significant effect on clinical and sub-clinical outcomes”, said Dr. Aaron Isaacs, who led the project. “In the future, as our knowledge of genetic variation increases, effective pre-clinical genetic screening tools may be able to enhance the prediction and prevention of diseases such as cardiovascular disease.”

New genetic variants influencing lipid levels are being identified all the time, the researchers say. “As new variants are discovered, we would like to be able to continue to test them, both singly and combined, for association with cardiovascular disease. The cost of these diseases to individuals, families, society and healthcare systems is immense”, said Dr. Willems.

“Cardiovascular disease is the main cause of death in Europe, killing over 4 million people per year. It also represents 23% of the total disease burden (illness and death) across the continent. Managing cholesterol levels is important for prevention. This can be done early in life by effective treatment. We hope that our study, showing that common genetic variants play an important role in the occurrence of cardiovascular disease, marks a starting point for early prediction and prevention and may thus reduce the burden of disease,” she concluded.

Traditional clinical risk factors can predict diabetes and heart disease already, but adding genetic tools to the mix could be useful, particularly in determining how aggressively to approach prevention in patients considered intermediate risk by conventional measures, commented Donna Arnett, PhD, MSPH, of the University of Alabama at Birmingham School of Public Health, and a spokesperson for the American Heart Association.

The cost of genetic testing could be a hurdle for clinical application, though, until ways are found to make it more affordable, she noted in an interview, adding lipodemic profiling is still in its infancy and more information is needed on how measures like dihydroceramide might measure up against clinical factors like waist circumference.

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The European Society of Human Genetics aims to promote research in basic and applied human and medical genetics, to ensure high standards in clinical practice and to facilitate contacts between all persons who share these aims, particularly those working in Europe. It currently has about 1600 members from 66 countries. About 2500 delegates are attending this year’s conference.

Note: These studies were published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Apples Reduce Bad Cholesterol (LDL) By 23%, Increase Good Cholesterol (HDL) By 4%, Finds New Study

APPLES are truly a “miracle fruit” that convey benefits beyond fiber content. Bahram H. Arjmandi of Department of Nutrition, Food and Exercise Sciences at The Florida State University in Tallahassee has found that eating an apple or two a day appears to lower levels of cholesterol and two other markers associated with plaques and inflammation in artery walls.

In his study, postmenopausal women who ate an apple a day gained heart healthy benefits and even lost weight in a study from food science researchers. In six-months, women age 45 to 65, lowered dangerous LDL cholesterol, raised beneficial HDL cholesterol levels and lost a few pounds from consuming dried apples. The study shows apples could be a heart healthy snack for everyone; not just women.

Indeed, the findings are of great interest to diabetics who must maintain tight control of their blood sugar levels every day. Uncontrolled diabetes puts them at greater risk for heart disease.

Arjmandi’s recent research is the first to evaluate the long-term cardioprotective effects of daily consumption of apple in postmenopausal women, says a news release. The results of the study, which were presented at Experimental Biology 2011 on April 12 in Washington, DC, should be considered preliminary as they have not yet undergone the “peer review” process, in which outside experts scrutinize the data prior to publication in a medical journal.

Arjmandi reported that “incredible changes in the apple-eating women happened by 6 months ‒ they experienced a 23% decrease in LDL cholesterol. The daily apple consumption also led to a lowering of lipid hydroperoxide levels and C-reactive protein in those women.  “I never expected apple consumption to reduce bad cholesterol to this extent while increasing HDL cholesterol or good cholesterol by about 4%,” he said.

Though the study used dried apples for convenience, Arjmandi said fresh are likely to be even better. And it doesn’t matter if they’re green, red, or golden. “Any varieties of apples are good,” he said.

Yet another advantage is that the extra 240 calories per day consumed from the dried apple did not lead to weight gain in the women; in fact, they lost on average 1.5kg (3.3lb). “Reducing body weight is an added benefit to daily apple intake” he said. Part of the reason for the weight loss could be the fruit’s pectin, which is known to have a satiety effect.

This study randomly assigned 160 women ages 45-65 to one of two dietary intervention groups: one received dried apples daily (75g/day for 1 year) and the other group ate dried prunes every day for a year. Blood samples were taken at 3, 6 and 12-months.

Experts said the study’s results were consistent with previous evidence that apples do indeed live up to the famous adage about keeping the doctor away.

“When we look at the whole composite of human studies and animal studies and in vitro lab studies, when you look at the active components in apples and apple juice, there’s definitely benefit,” Dianne A. Hyson, PhD, RD, a nutritionist and researcher at the University of California at Davis was quoted as saying in a WebMD Health News report.

Hyson, who was not involved in the current research, recently completed a review of 80 studies, published since 2005, on the health benefits of apples, and she said that in addition to their cardiovascular benefits, there’s some evidence that apples help regulate blood sugar and control appetite, protect against cancer, and safeguard the lungs.

Another key, Dyson said, is eating the whole fruit, rather than looking for individual components in supplements. “Most of the time, in many studies, the whole is better than the sum of its parts,” she said. As far as how much to eat, just follow the apple-a-day adage, though Arjmandi said two-a-day might be even better. “That’s doable and practical and people like apples,” he said.

The next step in confirming the results of this study is a multi-investigator nationwide study.

Source: Experimental Biology 2011 Onsite Newsroom

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Diabetes Management: Tight Cholesterol, BP Control Does Little Good for Diabetics

Lower isn’t always better in diabetes management. In fact, pushing too hard may not help, and may actually hurt in some cases. This has been proved, once again, by the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, results released last week reveal. Indeed, the new lipid and blood pressure results round out the negative portrait of aggressive risk factor management in diabetes patients.

(ACCORD is one of the largest studies ever conducted in adults with type 2 diabetes who were at especially high risk of cardiovascular events, such as heart attacks, stroke, or death from cardiovascular disease.  The multicenter clinical trial tested three potential strategies to lower the risk of major cardiovascular events: intensive control of blood sugar, intensive control of blood pressure, and treatment of multiple blood lipids. The lipids targeted for intensive treatment were high density lipoprotein (HDL) cholesterol and triglycerides, in addition to standard therapy of lowering low density lipoprotein (LDL) cholesterol. Read the Questions & Answers about the ACCORD Trial here.)

According to received wisdom, intensive blood pressure and blood fat management could drive down diabetics’ higher risks of heart problems. But results from the ACCORD trial prove that when it comes to traditional measurements of heart disease risk, a blood pressure target of 120 mm Hg rather than the general population standard of 140 did not reduce nonfatal heart attacks, nonfatal strokes or death from cardiovascular causes.

Likewise, adding the cholesterol-busting drug fenofibrate to standard statin therapy did not reduce the chances of major adverse cardiovascular events. Indeed, tribal behavior by physicians that is no doubt driven by the big pharma marketing machinery, has raised concerns about the ramifications of recommending costly medications that don’t confer real benefits to patients. (See my post ‘Increased Use of Fibrates in US Could Be A Triumph Of Marketing Over Medicine’ here.)

Both studies ‒ part of the complex ACCORD trial ‒ were presented at the American College of Cardiology meeting in Atlanta, Ga. and released simultaneously online in the New England Journal of Medicine.

[A third part of this research ‒ one which examined intensive lowering of blood sugar to see if this had a positive effect ‒ was prematurely halted in 2008 because it turned out that patients receiving this approach actually had an increased, instead of decreased, risk of death. (See a related post ‘Aggressive Diabetes Therapy May Raise Death Risk’ here.)]

As for the newly released findings, the lipid arm of ACCORD included 5,518 patients with high risk of heart problems because of cardiovascular disease or at least two risk factors. LDL, or bad, cholesterol levels had to be between 60 and 180 mg/dL; HDL, or good cholesterol, levels had to be under 50 mg/dL or 55 mg/dL for women and blacks; and triglycerides had to be under 750 mg/dL if the patients were not on any therapy, or 400 mg/dL otherwise. Patients either received fenofibrate or a placebo in addition to statins.

What the researchers found was that lipid and triglyceride levels responded as expected. Despite this, however, the patients appeared to receive no benefit when it came to major heart problems such as heart failure, stroke and nonfatal heart attacks.

Meanwhile, the  blood pressure portion of ACCORD compared a strategy of keeping systolic blood pressure under 120 mm Hg to one of under 140 mm Hg in 4,733 diabetes patients with high risk of cardiovascular events because of clinical or subclinical heart disease or at least two risk factors. In this trial, treatment effectively lowered blood pressure. But again, there was no impact on aspects of patient health including death risk, death related to heart problems and nonfatal heart attacks.

ABC News reported that the U.S. Food and Drug Administration will conduct a full review of findings from the ACCORD study. An FDA spokesperson said the agency planned to include a review of the labeling and indications for fenofibric acid (Trilipix) ‒ even though the trial used fenobrate (TriCor). Asked about the timing of the announcement, the spokesperson said the FDA was attempting to be more proactive.

Both Trilipix and TriCor are marketed by Abbott, and Trilipix is “the active metabolite of TriCor,” according to Dr. Marshall Elam of the Memphis VA Medical Center. Elam, who was involved in the design of the lipid treatment arm of ACCORD said that “neither TriCor nor Trilipix has a label indication for cardiovascular disease.”

In a statement released after the ACCORD results were reported, but before the FDA said it would conduct a review of the ACCORD findings, Abbott said the data from the ACCORD Lipid trial “supports the appropriate patient type and current treatment guidelines for fibrates. The top-line results of the study were widely expected, given that two-thirds of patients in the trial would not be recommended for fibrate therapy under current guidelines.”

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