Lifestyle determines risk for cardiovascular disease: Inflammation flagged as key

A study by researchers from the Broad Institute of MIT and Harvard have determined that “a set of genetic mutations in blood cells that arises during aging” can possibly be a major new risk factor for cardiovascular disease.

The researchers said that since the mutations are more common in older people (more than 10 percent of people older than 70 years old have at least one of these mutations), pending efforts to “screen for the mutations in blood cells, identify people at increased risk for coronary heart disease, and reduce risk in those individuals through lifestyle changes or therapeutic interventions” might have a notable clinical impact.

Benjamin Ebert, a co-senior author of the new study and an institute member at Broad, explained, “There is more work to be done, but these results demonstrate that pre-malignant mutations in blood cells are a major cause of cardiovascular disease that in the future may be treatable either with standard therapies or new therapeutic strategies based on these findings.”

The study can also help further the current understanding of pathogenesis in coronary heart disease by supporting the hypothesis that inflammation, along with elevated cholesterol levels, has an important role in this illness and, possibly, other aging-related diseases.

Siddhartha Jaiswal, the study’s first author and a pathologist at Massachusetts General Hospital and researcher in the Ebert lab, commented, “A key finding from this study is that somatic mutations are actually modulating risk for a common disease, something we haven’t seen other than in cancer.”

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Jaiswal continued, “It opens up interesting questions about other diseases of aging in which acquired mutations, in addition to lifestyle and inherited factors, could modulate disease risk.”

An earlier study led by Ebert and Jaiswal has determined that some somatic mutations that are able to confer a selective advantage to blood stem cells increases in frequency as a person ages. The condition, which they named “clonal hematopoiesis of indeterminate potential” (CHIP), “increases the risk of developing a blood cancer more than 10-fold.” CHIP also allegedly increase mortality from heart attacks or stroke.

Atherosclerosis is described as a disease of chronic inflammation that occurs due to excess cholesterol in the vessel wall. To study this on a cellular level, the team looked into the macrophage, an immune cell in atherosclerotic plaques that can develop from CHIP stem cells and have the same mutations. Since Tet2 (one of the CHIP-mutated genes) and other CHIP-related mutations are also “epigenetic regulators” which can alter the activity of other genes, the team studied gene expression levels in the Tet2-mutated macrophages from mice. The mutated cells were “hyper-inflammatory” with increased expression of inflammatory molecules that contribute to atherosclerosis. This could mean that individuals with TET2 mutations also had higher levels of one of these molecules, IL-8, in their blood.

Co-senior author Sekar Kathiresan, director of the Broad’s Cardiovascular Disease Initiative, associate professor of medicine at Harvard Medical School, and director of the Center for Genomic Medicine at Massachusetts General Hospital, shared, “By combining genetic analysis on large cohorts with disease model and gene expression studies, we’ve been able to confirm the earlier hints of CHIP’s surprising role in cardiovascular disease.”

Kathiresan concluded, “Beyond the mutations that you inherit from your parents, this work reveals a new genetic mechanism for atherosclerosis — mutations in blood stem cells that arise with aging.”

Natural ways to prevent heart disease

These tips can help prevent cardiovascular disease:

  • Quit smoking and avoid second-hand smoke – Cigarette smoking and second-hand exposure to smoke increase the risks of heart disease, lung disease, peripheral vascular disease, and stroke.
  • Monitor your blood pressure – High blood pressure, or hypertension, is “the silent killer” because most people don’t show any symptoms.
  • Minimize the calories you consume – Practice portion control, limit your sugar intake, and drink lots of water.
  • Exercise regularly – Simply walking two miles daily can help you stay in shape.

You can read more articles about natural ways to prevent heart disease at

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