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2021 Study: Existing Drug Reduces Risk of Fatal Cardiovascular Disease



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Elevated levels of lipids known as ceramides can be associated with a
ten-fold higher risk of death from cardiovascular disease.
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https://news.ki.se/weight-loss-treatment-prevents-accumulation-of-lipid-linked-to-cardiac-mortality
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Obesity is one of the greatest risk factors for cardiovascular diseases such as myocardial infarction and stroke. The World Health Organization (WHO) has estimated that cardiovascular diseases are the main cause of mortality worldwide, resulting in more than 17 million deaths a year. Principal investigator in the Department of Medical Biochemistry and Biophysics at the Karolinska Institute, Craig Wheelock said "Understanding the link between obesity and cardiovascular diseases is important and can lead the way to the development of new therapies."
Fat has traditionally been seen as simply storage tissue, but in recent years it has been shown to be a "biochemical laboratory" capable of producing signaling molecules that control potent biological functions. Understanding how adipocytes produce and release these molecules opens the possibility of reprogramming them, with the aim of preventing future incidence of cardiovascular disease. Using a mass-spectrometer the Wheelock Laboratory was able to measure levels of multiple metabolites secreted by two kinds of human fat tissue. The fat that accumulated around the heart in obese individuals secreted different metabolites relative to subcutaneous fat. In obese individuals the fat that surrounds the heart, secreted higher levels of ceramides. In particular, elevated levels of a specific lipid variant called C16:0-ceramide were observed, this is a based on palmitic acid, which is a saturated fat consisting of 16 carbon atoms. The researchers were also able to show that ceramides secreted from adipose tissue damaged human blood vessels by initiating a process called oxidative stress, which can eventually lead to heart attacks and stroke.
Assistant Professor Craig Wheelock stated that "These results show emphatically that fat is not just energy-storage tissue but also a source of important bioactive molecules that can have powerful immunomodulatory functions. In addition, all tissue is not equal, and the type of fat is clearly important in determining the observed biological function."
To understand the significance of the cardiovascular effects of the ceramides, the researchers studied 633 patients with atherosclerosis; they were monitored for more than five years. They found that elevated levels of both C16:0-ceramide and its glycosylated variant could be linked to a ten-fold increase in the risk of fatal cardiovascular disease, even after controlling for other risk factors including age and weight.
Co-author Antonio Checa, the researcher who conducted the analyses said "The results suggest that it could be worth incorporating the measurement of different kinds of sphingolipids, both in their original form as well as the glycosylated variants, to better gauge the risk of the occurrence of a fatal cardiovascular event."
In the last part of the study, 32 volunteers were placed on a low-calorie diet for eight weeks before being split into two groups, one group received a placebo and one received a GLP 1-analog drug that is approved for the treatment of obesity and type 2 diabetes. Both groups continued the low-calorie diet for another 44 weeks. One year after the study ceramide levels in the blood had increased significantly in the control group, while levels remained stable in the group taking the GLP 1 analog drug.
principal investigator Craig Wheelock said "The most important findings are that we add to the evidence that there is a direct correlation between risk of fatal cardiovascular disease and ceramide levels in the blood, and that this can be treated with an existing medication."
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#CardiovascularDisease #Ceramides #Atherosclerosis #Statins #BloodPressure #HeartAttack #livelonger #livelong #Aging #Lifespan #healthspan #weightloss #nutrition #fat
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