Researchers seek clues to high blood pressure's origins, impacts

How high blood pressure develops and the effects it has on the body are the focus of a two-part study under way at Penn State and Johns Hopkins University that will look at hypertension in the human body and in the laboratory.

"One quarter of the population in the United States has undiagnosed or is being treated for essential hypertension," said Lacy Holowatz, assistant professor of kinesiology, who is the principal investigator on the project. "Not only is it pervasive, but it takes an emotional, physical and financial toll on the people it affects. The results from our studies should provide new and important information on the how hypertension impacts the body's cardiovascular system."

The National Heart, Lung and Blood Institute of the National Institutes of Health will fund this five-year study for $1.7 million. The NIH's American Recovery and Reinvestment Act funding will supply $750,000 of the grant.

Essential hypertension, also known as primary hypertension, is high blood pressure with no identifiable cause. Secondary hypertension, in contrast, is high blood pressure that results from another condition or disease.

The research team will use a dual-examination approach analyzing hypertension and blood flow in the body and, in a more controlled situation, outside the body. The human studies will take place on Penn State's University Park campus and will use microdialysis, a method where researchers insert a microfiber into a portion of skin about the size of a quarter and infuse certain drugs or solutions to only that area. For the external examination, Holowatz will work with researchers from the Johns Hopkins University who will analyze skin biopsy samples.

Holowatz will heat and cool the skin to examine blood vessel function. She will see how this differs in someone with hypertension compared with someone with normal blood pressure. Holowatz's aim is to shed light on potential therapeutic strategies for people with hypertension. The work is an extension of previous work by Holowatz and her colleagues that provided a better understanding of how hypertension affects the body's vascular system.

Other key individuals working on the project include Larry Kenney, professor of physiology and kinesiology; Mosuk Chow, associate professor of statistics, and Jane Pierzga, research assistant, all at Penn State, and Daniel Berkowitz, associate professor of anesthesia and critical care medicine at Johns Hopkins University.

Road noise link to blood pressure

People living near noisy roads are at greater risk of developing high blood pressure, a Swedish study suggests. A Lund University team found risk rose above an average daily exposure of 60 decibels, which accounts for about one in four people in western Europe.

They said it was likely noise caused stress - and maybe sleep disruption - leading to blood pressure problems. But UK experts questioned the findings, saying other factors such as diet and smoking were more important. Researchers analysed questionnaires completed by nearly 28,000 people as well as analysing neighbourhood traffic noise. They found that at above 60 decibels the risk of high blood pressure rose by more than 25%.

Above 64 decibels the risk rose by more than 90% although the team cautioned that the low numbers in this group could have skewed the findings. The report, published in the Environmental Health journal, said the findings were worrying as high blood pressure increased the chances of heart disease and stroke.

However, the link was not apparent for people above 60 years old. The researchers said this was either because they had become desensitised to the noise or already had high blood pressure.

Report author Theo Bodin said: "Road traffic noise is the most important source of community noise so we felt it was important to look at this. "I think what we have found is probably linked to the noise triggering stress. Previous research has found this, although we need to look at this issue further before we make firm conclusions."

But Professor Alan Maryon-Davis, president of the UK's Faculty of Public Health, said: "It seems to me that they have found an association rather than a cause. Other factors, such as smoking, diet and deprivation, are likely to be playing more of a role.

"However, it is an area of research which merits further work."

Source: BBC

Only 3 cigarettes a day significantly increases cardiovascular disease

Exposure to relatively low levels of fine particulate matter (PM) significantly increases the risk of cardiovascular disease [1]. The risk trajectory levels off with higher levels of exposure, researchers report, in a study published online August 31, 2009 in Circulation. The study will appear in the September 15 issue.

Risk of cardiovascular disease increased 64% by smoking three cigarettes a day. Risk doubled by smoking a pack a day, according to data on more than one million adults prospectively collected by the American Cancer Society, as part of the Cancer Prevention Study II of 1982.
Using this database, Dr C Arden Pope (Brigham Young University Provo, UT) and colleagues calculated adjusted relative risks of mortality according to an estimated average daily dose of fine PM from active cigarette-smoke inhalation, as well as the PM doses from secondhand cigarette-smoke exposure and from exposure to air pollution.

"There were substantially increased cardiovascular mortality risks at very low levels of active cigarette smoking and smaller but significant excess risks even at the much lower exposure levels associated with secondhand cigarette smoke and ambient air pollution," the researchers report. "The results indicate that it is fundamentally implausible that the relationship between cardiovascular mortality and fine particulate pollution from cigarette smoke and ambient air pollution can be characterized as linked by a simple linear dose-response relationship," the authors write. "Rather, our results suggest that the exposure-response function is relatively steep at very low levels of exposure, flattening out at high exposure levels."

Pope and colleagues note several limitations of the study, among them the large exposure gap between ambient air pollution, secondhand-smoke exposure, and active smoking. And, the authors say, there are no prospective cohort or related studies of long-term exposure across the range of exposure that would fill this gap.

Even with its limitations, the study findings have important public-health implications, Pope's team comments. Most studies of the effects of fine PM on cardiovascular disease risk have been conducted in areas where the annual average PM concentrations rarely exceed 30 µg/m3. Recent estimates indicate average concentrations of particulate air pollution in urban areas of China, India, and other developing countries often exceed 100 µg/m3.

Source: http://www.theheart.org/article/999851.do

Information about how fat causes high blood pressure

Some of the first information about how fat causes hypertension have been identified by researchers who say the findings should one day help identify which obese people - and maybe some thin ones too - are at risk for hypertension and which drugs would work best for them.

Medical College of Georgia researchers have found that deleting or mutating the gene PTP1B puts mice at risk for hypertension by interfering with an endogenous mechanism that should help prevent it. The findings are published in the Sept. 1 issue of the American Heart Association journal Circulation.

"In a normal individual gaining weight, PTP1B should increase and they would be protected in theory from hypertension," says Dr. David Stepp, vascular biologist at the MCG Vascular Biology Center, co-director of the Diabetes & Obesity Discovery Institute and the study's corresponding author.

"But if you don't have a good copy of PTP1B and you become obese, then you are going to have a problem. So in theory this gene can segregate the obese people who will become hypertensive and those who won't."

Knowing the gene's status could also one day help physicians better select an antihypertensive medication for those who do.

A key player is the hormone leptin, produced by fat cells. Overweight individuals generally produce more of the hormone that essentially revs up the body, suppressing appetite and increasing metabolism so you won't get fatter. But leptin also increases blood pressure by activating the sympathetic nervous system, the so-called fight-or-flight response. Mutated or missing PTP1B dramatically increases leptin's negative effects.

MCG scientists studying how blood pressure got the message to increase found leptin also provides protection against high pressures by turning off the signaling pathway that squeezes blood vessels and drive pressures up in a process called adrenergic desensitization.

"Normally, if you give someone leptin, his blood pressure would probably not go up because he would have this protective mechanism intact that would basically turn off his blood pressure signaling pathway," Dr. Stepp says. "His blood pressure would be regulated differently, but it would not be high."

But the combination of missing or mutated PTP1B and too much leptin means increases in constriction are too strong to turn off.

Mice missing PTP1B tend to have lower body fat but high blood pressure, not usually what you see in people, Dr. Stepp notes. While this single gene can't explain every combination of body size and blood pressure found in nature, it could help explain why some skinny people are hypertensive and why others who get fat are as well.

"It's a vulnerability gene," he says. "If you stimulate leptin in individuals who can't activate their protective mechanisms, they are going to get hypertension. This tells us there are a lot of people and diseases

And what about those people who have great blood pressure? They likely have well-functioning PTP1B, he notes. Interestingly, PTP1B often is over expressed in obese people, which is good for the blood pressure but bad for leptin's positive effect on metabolism.

"I think we have identified at least a couple of new pieces of information that clarify the relationship between obesity and hypertension," Dr. Stepp says. "We have identified a gene that, if it's not functional, will greatly increase the extent to which a metabolic signal from leptin translates into a cardiovascular signal. We also have identified a protective mechanism that, if it's not working, contributes to hypertension."

The MCG research helps illustrate the need to pay particular attention to the cardiovascular side effects of potential new anti-obesity drugs as well, experts say. In an accompany editorial, Dr. Allyn L. Mark, Carver Professor of Medicine, Center on Functional Genomics of Hypertension at the University of Iowa Carver College of Medicine, noted the irony that despite lower body fat, mice with disturbed PTP1B had higher blood pressure than control animals. "Unfortunately several of the interventions that inhibit appetite, increase metabolism and decrease adiposity (fat) may increase (not decrease) sympathetic activity and arterial pressure," he writes. "This may complicate the safety of potential anti-obesity drugs," and emphasizes the importance of evaluating the cardiovascular impact of potential new therapies.

Now MCG scientists want to develop markers so one day people determine their PTP1B expression through a blood test. They also want to learn more about exactly how leptin increases blood pressure to see if there are ways to target some of the downstream impact of missing or mutated PTP1B.

"We want to look the impact on the kidneys and angiotensin 2," says Dr. Eric J. Belin de Chamtemèle, postdoctoral fellow in Dr. Stepp's lab and the study's first author. The kidneys, which determine how much sodium and water are excreted from the body, are major players in blood pressure regulation. Renin, which is secreted by the kidneys, constricts blood vessels to help blood pressure increase when blood volume gets low.

They want to know if leptin is acting directly on the kidneys or whether it's an indirect result from leptin's action in the brain. They suspect it's primarily a brain effect that they want to pursue by using mice with leptin deficits localized to the brain.

Source: Mednews / Toni Baker Medical College of Georgia

Patient race more important than blood pressure control status for determining the quality of patient-doctor communication

Patient race more important than blood pressure control status for determining the quality of patient-doctor communication

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European Society Releases Guidelines for Pediatric Hypertension

The European Society of Hypertension has issued guidelines for managing high blood pressure in children and adolescents. The guidance was issued to fill a gap left by the exclusion of the topic in the latest adult guidelines from the ESH and the European Society of Cardiology, according to a committee led by Empar Lurbe, MD, of the University of Valencia in Spain.

Although many of the recommendations are made on the basis of expert consensus, owing to the lack of randomized data, they said "it would be unethical to neglect giving due attention to this medically and socially important problem." They said the guidelines, published in the September issue of the Journal of Hypertension, "should encourage public policymakers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents."

Normal blood pressure for children younger than 18 was defined as less than the 90th percentile according to age, sex, and height. This should be the target for treatment for most children with elevated blood pressure, according to the guidelines. A child is considered hypertensive with measurements in the 95th percentile or higher on at least three occasions. Measurements between the 90th and 95th percentiles are considered high-normal.

According to the guidelines, the auscultatory method should be used to measure blood pressure, which should be done in all children older than 3 and in younger children when special circumstances place them at risk for high blood pressure.

The authors said 24-hour ambulatory blood pressure monitoring should be used to confirm a diagnosis of hypertension before initiating treatment. The first steps following a diagnosis should involve the recording of a family and clinical history, a physical examination, a cardiovascular examination, and a neurological examination, they said. This should be followed by routine blood tests and tests for plasma renin activity, plasma aldosterone concentration, urine and plasma catecholamines or metanephrines, and urinary free cortisol, as well as a Tc99 dimercaptosuccinic acid scan.

In addition, children should be evaluated for organ damage, specifically in the heart, great vessels, kidneys, central nervous system, and retina, the authors said. This process will help identify any secondary causes of hypertension that require treatment.

The guidelines contained the following additional recommendations for managing a pediatric patient with hypertension:

First target the risk factors for elevated blood pressure, including overweight, increased salt intake, and low physical activity. Body mass index should be kept below the 85th percentile.

• Regular exercise and a well-balanced diet are recommended. These measures should be continued even when drug treatment is started.
• Pharmacological treatment should be started when patients have symptomatic hypertension, hypertensive target organ damage, secondary hypertension, or diabetes at the time of presentation.
• For children with chronic kidney disease, blood pressure should be lowered below the 75th percentile if they do not have proteinuria, and below the 50th percentile if they do have proteinuria. Combination drug treatment might be necessary.
• When initiating drug treatment, start with a low dose of a single drug. If there is no response within a few weeks, increase to a full dose.
• If the initial drug does not work, try a drug in a different class. In pediatric studies, all drug classes resulted in similar blood pressure reductions, but ACE inhibitors and angiotensin receptor blockers are the most widely used.

The authors acknowledged that there was little data from randomized clinical trials guiding the recommendations and said there was an urgent need for studies establishing doses and addressing the advantages and disadvantages of individual agents in pediatric patients.

In addition, they called for further research to obtain reference values for office, home, and ambulatory blood pressure, to collect information about early organ damage in hypertensive children, and to provide information about when to initiate pharmacologic treatment and which targets to meet.

Source: Medical News Europe / Journal of Hypertension

Glucose intolerance in pregnancy may be an indicator of cardiovascular risk

Mild glucose intolerance in pregnancy may be an early identifier of women who are at increased risk of heart disease in the future, found a new study published in CMAJ (Canadian Medical Association Journal).

In a large population-based cohort study, researchers from the University of Toronto and the Institute for Clinical Evaluative Sciences (ICES) studied data on 435,696 women in Ontario, Canada, who gave birth between April, 1994 and March, 1998. All women were followed until March 31, 2008. The study excluded women with pre-existing diabetes.

As cardiovascular disease is the leading cause of death in Canadian women, it is important to identify early predictors of future vascular risk. While women with gestational diabetes have a higher risk of cardiovascular disease than those without, it previously has not been known whether mild glucose intolerance in pregnancy is associated with heart disease. The study sought to answer this question.

Gestational diabetes is a condition leading to temporarily high blood sugars during pregnancy. It is an important risk factor for future type 2 diabetes. Women are generally screened for gestational diabetes with a glucose challenge test in the late second trimester. If the result is abnormal, they go on to have an oral glucose tolerance test to confirm the diagnosis.

"Women who had an abnormal glucose challenge test but then did not have gestational diabetes had an increased risk of future cardiovascular disease compared to the general population, but a lower risk than women who actually did have gestational diabetes," writes Dr. Baiju Shah, Institute for Clinical and Evaluative Sciences and coauthor.

They suggest that "in women with glucose intolerance during pregnancy, type 2 diabetes and vascular disease may develop in parallel, which is consistent with the "common soil" hypothesis for these conditions." Current screening procedures for gestational diabetes might also provide a means for the early identification of women who are at risk for developing heart disease later in life.

In a related commentary Dr. J. Kennedy Cruickshank and Dr. Moulinath Banerjee of the Manchester Royal Infirmary, University of Manchester, UK write that "what the study by Retnakaran and Shah shows is that we all have a great deal to learn from sub-clinical blood vessel changes in younger women who are likely overweight during pregnancy."

They suggest that diabetes research should focus on the blood vessel rather than glycemia.

Source: Science Daily