Gene Finding Lends Clues to Blood Pressure Problems
A new genetic discovery may help explain why some people develop high blood pressure and others do not, and why some people's blood pressure increases as they age, according to a report in the American Journal of Hypertension.
The findings also give new insight into how the kidneys govern the balance of salt in the body, a crucial task for regulating blood pressure.
And, it reveals how a gene already linked to behavior and mental health can play a role in the body, as well as the brain.
The researchers say that one in four adults in the US has high blood pressure, also called hypertension - and many do not know it.
If high blood pressure is not lowered with the help of diet, exercise, and medication, it can dramatically raise the risk of heart attack, stroke, or kidney problems.
Blood pressure, measured with a blood pressure cuff and stethoscope by a nurse or other healthcare provider, is the force of the blood pushing against the artery walls. Each time the heart beats, it pumps blood into the arteries, resulting in the highest blood pressure as the heart contracts.
Two numbers are recorded when measuring blood pressure. The higher number, or systolic pressure, refers to the pressure inside the artery when the heart contracts and pumps blood through the body.
The lower number, or diastolic pressure, refers to the pressure inside the artery when the heart is at rest and is filling with blood.
Both the systolic and diastolic pressures are recorded as "mm Hg" (millimeters of mercury). This recording represents how high the mercury column is raised by the pressure of the blood.
Individuals are considered to have high blood pressure if their blood pressure is greater than 140 mm Hg systolic, or 90 mm Hg diastolic.
The researchers report that in the study, blood pressure was higher and more likely to rise with age among persons who had an extra-long form of a gene called DRD4.
They made the discovery by studying the genes of 864 people from 286 families taking part in a long-term blood pressure genetics study called GenNet.
The families all live in or near the town of Tecumseh, Mich., which since 1958 has been home to a U-M clinical research initiative called the Tecumseh Community Health Study.
The finding of a link between DRD4 and blood pressure came as a surprise to researchers who tested this gene initially to look at genetics and behavior.
Cells use the DRD4 gene to make a receptor for a chemical called dopamine, which transmits messages between cells.
Dopamine is best known for its role in the brain, where it is involved in feelings of pleasure, and in governing movement.
Some studies have suggested that variations in genes for dopamine receptors are linked to certain behavioral traits or personality types.
But in recent years dopamine has also been found to play a role in regulating the release of salt by the kidneys. The new finding adds more evidence for that role.
"While many genes are involved in blood pressure and the inherited risk of developing hypertension, we're learning that variations in genes for dopamine receptors play a significant role," says senior author Dr. Alan Weder, professor of internal medicine at the University of Michigan Medical School.
"As we learn more, we may be able to determine which patients need the most aggressive blood pressure treatment, and to develop drugs that can lower blood pressure by intervening directly in the proximal tubules of the kidneys, where dopamine acts - something today's drugs don't do," Dr. Weder explains.
The new study is the first to show that the DRD4 receptor plays a role in the regulation of blood pressure by the kidneys, and to show that a common variation in the gene is associated with higher blood pressure.
Two other dopamine receptors have previously been shown to be linked to blood pressure regulation.
Blood pressure, especially the systolic pressure, tends to rise as a person gets older. And in older people, high systolic pressure is considered the greatest risk factor for cardiovascular disease.
That is one reason the new finding is especially significant, says Dr. Weder.
"This gene variation may be useful in developing a predictor of which patients are likely to have a rapid rise in blood pressure as they age, and may need more aggressive monitoring and treatment," he says.
However, he and his co-authors say, no one gene variation is enough to predict an individual person's blood pressure tendencies, and further research on the genes involved in hypertension will be needed.
The other important implication of the finding is to create a fuller understanding of dopamine's action in the kidneys, and changes in that action brought about by variations in the receptor gene.
Dopamine in the kidney helps the body respond to large loads of sodium, or salt, coming into the body.
After a salty meal, for example, higher levels of dopamine can be detected in the urine after being produced and used by the kidneys to regulate the removal of salt from the body.
Always consult your physician for more information.
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The use of medicated stents markedly improves the clinical outcomes of patients who develop blockages in aging veins surgically grafted onto the heart, according to a report in Catheterization and Cardiovascular Interventions.
The Society for Cardiovascular Angiography and Intervention's journal reports that compared to conventional bare metal stents, drug-eluting stents significantly cut the rates of heart attack and repeat procedures, both of which are indicators of renarrowing - or restenosis - within the stent.
Maintaining blood flow to the heart through aging vein grafts clogged with cholesterol plaque, blood clots, and other debris is especially challenging, the researchers say.
"There was a fourfold reduction in the incidence of restenosis with the medicated stents," says Dr. Raj Makkar, co-director of the Cardiovascular Intervention Center at Cedars Sinai Medical Center in Los Angeles. "At least over the short term, that's very encouraging."
Drug-eluting stents slowly release medication that prevents the overgrowth of scar tissue inside the stent, and have been shown to significantly reduce the risk of restenosis in the natural arteries of the heart.
Treating worn and diseased vein grafts is more challenging, however. In fact, within five to 10 years, half of all vein grafts become diseased, necessitating either stenting or repeat bypass surgery in some cases.
The study analyzed data from 223 consecutive patients who had a stenting procedure to restore blood flow through clogged vein grafts, 139 of whom were treated with a drug-eluting stent and 84 of whom were treated with a bare metal stent.
Patients had undergone the original bypass surgery an average of nearly 8 years earlier.
During nine months of follow-up, 4 percent of patients treated with a drug-eluting stent experienced a heart attack, as compared to 20 percent of patients treated with a bare metal stent.
Similarly, 10 percent of patients treated with a drug-eluting stent needed a repeat procedure to reopen the vein graft, as compared to 37 percent of patients treated with bare metal stents.
The combined rates of heart attack, repeat procedure, and death were 10 percent and 37 percent, respectively.
The Cedars Sinai researchers are continuing to follow-up patients to determine whether drug-eluting stents offer a similar advantage over the long run.
Since plaque tends to build up throughout vein grafts, patients may develop new blockages that require additional stenting procedures.
"We can't expect drug-eluting stents to eliminate all problems with bypass grafts, but this study suggests it is reasonable to use medicated stents to treat these patients," Dr. Makkar says.
Always consult your physician for a diagnosis.
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American College of Cardiology
American Heart Association
American Journal of Hypertension
Centers for Disease Control and Prevention (CDC)
Go Red for Women Campaign, AHA
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
National Library of Medicine
National Women's Health Information Center
Society for Cardiovascular Angiography and Intervention
US Health and Human Services
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