Heart-Healthy Lifestyle Changes Also Alter Gene Expression

Marlene Busko

March 05, 2014

WINDBER, PA — After a yearlong, intensive diet, exercise, and stress-management program to reduce cardiovascular risk factors, participants who successfully followed the program and lost weight also had positive changes at the molecular level, researchers report[1].

"What's really new and important about this study is that throughout a year of lifestyle changes, you do not just make physical changes—like lowering weight and reducing your blood pressure—but you are making a number of molecular changes as well, and those molecular changes are really associated with the [improved] health of your vasculature," lead author Dr Darrell L Ellsworth (Windber Research Institute, Windber, PA) told heartwire .

However, just as people who don't stick to a diet and exercise program may start gaining weight again, these molecular-level changes were transient, which emphasizes the importance of making lifelong healthy choices.

"This [study] further reinforces that lifestyle changes are beneficial" and need to be maintained, he said.

The study was published online February 22, 2014 in Circulation: Cardiovascular Genetics.

Delving Deeper Into Molecular-Level Changes

Although lifestyle changes are believed to lower CVD via pathways that affect endothelial function and progression of atherosclerosis, little is known about effects at a molecular level, the researchers write. "Many researchers have examined short-term changes in gene expression in response to diet or exercise, but no one has really examined these changes during a lifestyle program for reversing heart disease," Ellsworth said.

Patients who entered the program either had or were at high risk for developing heart disease, and they were highly motivated to try to reduce their CV risk by following this healthy diet, exercise, and stress-reduction program—to try to decrease the number of medications they were taking and avoid invasive procedures like a stent, angioplasty, or a coronary bypass, Ellsworth explained.

"We could see that if they adhered to the program, they would lose weight, their blood pressure would drop, their lipid levels would go down, and they would feel better. We were interested in what molecular changes were occurring."

They examined the impact of their CVD risk reduction program on the gene-expression profiles in peripheral blood samples—at baseline, 12 weeks, and one year—in 63 participants in the program and 63 controls matched for age, gender, and CVD status.

At study entry, the participants had CAD or two or more risk factors for CAD (hypertension, high total cholesterol, diabetes, obesity, or a family history of heart disease). The controls received standard care from their primary-care physicians. The patients had a mean age of 60.3 years (range 44.5–78.4).

The lifestyle-change program consisted of:

  • A very low-fat vegetarian diet (<10% of calories from fat).

  • 180 minutes/week of moderate aerobic exercise.

  • One hour of stress management each day.

  • Weekly group support sessions.

Among participants in the lifestyle-change program, at one year, the prevalence of hypertension dropped from 41% to 17%. Similarly, the rate of obesity dropped from 60% to 37%, and the rate of dyslipidemia fell from 54% to 37%.

These participants had a dramatic 60% lower daily fat intake and a 38% improvement in physical fitness. This was reflected in a 9% improvement in BMI, a 7% drop in triglycerides, and a 7% drop in blood pressure.

Beneficial Effects on Vascular System

The researchers obtained peripheral blood samples from the participants and controls, isolated the RNA, and then used Gene Chip (Affymetrix) human genome arrays to analyze which genes were being turned on or off. They profiled about 22 000 genes.

"After a year of this lifestyle program, we saw 143 genes that really showed a significant change in their expression," Ellsworth said. "A lot of these genes were involved in the immune response. Most of these genes [99] were being downregulated, which is a sign that the amount of vascular inflammation was decreasing with this program."

In contrast, the control study subjects showed little change in the cardiovascular risk markers or in gene expression at one year.

"The number of significantly altered genes increased more than fivefold from week 12 to week 52, suggesting that patients who maintain healthy lifestyle behaviors over longer periods of time are likely to experience more diverse molecular change than patients participating in shorter-term activities," the researchers note.

The patients were taking 79 different CVD medications at baseline, which might have affected the results. However, this potential interference was ruled out, since changes in gene expression were similar whether or not participants received new medications during the study.

"Successful and sustained modulation of gene expression through lifestyle changes may have beneficial effects on the vascular system not apparent from traditional risk factors," Ellsworth and colleagues conclude. A possible mechanism is that "healthy lifestyles may restore homeostasis to the leukocyte transcriptome by downregulating lactoferrin and other genes important in the pathogenesis of atherosclerosis."

The researchers report no conflict of interest. The study was supported by the United States Army Medical Research and Material Command/Telemedicine and Advanced Technology Research Center and the Henry M Jackson Foundation for the Advancement of Military Medicine.

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