The finding suggests that ACE (angiotensin converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) could be valuable tools for treating or preventing post-traumatic stress disorder.

The results were published online May 1 in the Journal of Clinical Psychiatry.

“These results are particularly exciting because it’s the first time ACE inhibitors and ARBs have been connected to PTSD, and it gives us a new direction to build on,” says senior author Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory University School of Medicine and a researcher at Yerkes National Primate Research Center.

“These data come from an observational study, not a randomized clinical trial, so it is important to limit our interpretation until larger, placebo-control, double-blinded trials can be performed. Still, they provide evidence from a human population that could be followed up in a rigorous controlled trial. This class of medications has been widely prescribed for hypertension for years and their safety profiles are well known, so our results could be translated into action relatively quickly.”

The findings emerge from the Grady Trauma Project, an observational study of more than 5,000 low-income Atlanta residents with high levels of exposure to violence and physical and sexual abuse, resulting in high rates of civilian PTSD.

All 505 participants in this study were exposed to at least one traumatic event, and around 35 percent of them (180) met the criteria for diagnosis with PTSD. Out of 98 participants taking ACE inhibitors or ARBs, generally for the primary purpose of blood pressure control, 26 had a PTSD diagnosis.

People with PTSD can experience three types of symptoms: hyperarousal, avoidance/numbing, and intrusive thoughts. All the participants in the study reported how often they experienced these symptoms and the responses were compiled into a PTSD symptom score.

SAN DIEGO— Heart failure is the most common cause of death throughout the world, typically the result of chronic high blood pressure, also known as hypertension. As a result, research efforts have focused on an array of approaches aimed at preventing and treating high blood pressure. Recently, Japanese researchers examined the utility of an anti-hypertensive drug, moxonidine, which acts on the imidazoline receptors in the cardiovascular center of the brainstem. They found, using an animal model, that the drug can improve heart function and survival independent of its effect on blood pressure. They also found the drug had a favorable effect on oxidative stress, which is related to insulin resistance, the underlying abnormality in diabetes, which is common in people with heart failure.

An abstract presentation about the findings will be offered at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center. The study was conducted by Yoshitaka Hirooka, Nobuhiro Honda, Ryuichi Matsukawa, Koji Itou and Kenji Sunagawa, all of the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences in Fukuoka, Japan. It is entitled, “Central sympathoinibition improves left ventricular function during the transition from hypertrophy to heart failure in Dahl salt-sensitive rats.” The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

Heart failure is a chronic disease that takes many forms and a variety of medications are used to treat it. Drugs such as ACE inhibitors and beta blockers target the causes of systolic heart failure. Clonidine, a first-generation central sympathoinhibitory drug, targets brain receptors that reduce cardiac output and lower blood pressure. Moxonidine, a second-generation drug, targets diastolic heart failure and function by reducing the effect of the central nervous system (CNS) receptors to decrease sympathetic activation and thus reduce blood pressure. In the study, salt-sensitive, hypertensive rats either received Moxonidine or were assigned to the control group. Researchers later found that the animals who received the drug had a marked inhibition of the sympathetic activity (an area of the brain) compared to those that did not. The findings suggest that inhibition of the central sympathetic outflow is important in the mechanism of hypertension. According to Dr. Hirooka, “The findings are important because they suggest that moxonidine may be useful in targeting the central receptors in the brain that are known to occur in patients with hypertension.”

Next Steps

The study is the latest in a series conducted by the research team whose focus is on neural control of circulation in hypertension and heart failure. Looking ahead, they will work to identify the precise mechanisms involved in the beneficial effect of moxonidine, Dr. Hirooka said. They will also study other ways to see if the compound is a possible therapeutic tool for hypertensive heart disease to prevent heart failure. As the drug had beneficial effects on insulin resistance, they would like to further investigate the issue, he added.

Maxonidine is available in select countries in Europe and Asia. It is not currently available in the United States.

from Eurekalert 4/23/2012

A 25 per cent increase in high blood pressure screening in 19 developing countries would reduce the number of cardiovascular disease (CVD) events and deaths that occur each year by up to 3 per cent in these countries. The preliminary data presented today at the World Congress of Cardiology are the first findings from a new report from Harvard that will be published later this year.

The study found that around 900 million people in developing countries have high blood pressure but that only one-third are aware of their disease. Moreover, only 100 million of these people receive treatment, while only 5 per cent of the total are controlled.

Against this backdrop, this study was designed to assess the cost-effectiveness of an intervention to increase screening by 25 per cent in developing countries using a non-lab screening tool to treat those with a systolic blood pressure of greater than 140 mmHg and CVD risk of greater than 20 per cent.

The study found that screening an additional 25 per cent of the population would lead to an increase of more than 10 per cent in the rate of appropriate treatment of hypertension in high-risk individuals. The intervention would lead to about a 1-3 per cent reduction in CVD events and deaths. Furthermore, the incremental cost-effectiveness ratios of these screening programs were found to be well below one times GDP per capita in the 19 developing countries assessed.

“Strategies to increase the screening for hypertension could lead to significant reductions in CVD deaths, at costs that are considered to be acceptable according to WHO recommendations,” said Dr. Thomas Gaziano, assistant professor, Harvard School of Medicine.

From Eurekalert: 4/21/12

The authors argue that the findings – while in human pancreatic islets and diabetic mice – could have clinical implications as physicians consider that calcium channel blockers may address two major, related diseases. They also found evidence in past clinical trials that the study drug verapamil may slow diabetes.

Beta cells secrete insulin to control blood sugar levels, but begin to die as patients develop Type 1 or Type 2 diabetes. No one suspected that calcium channel blockers might reverse beta cell death because the studies that led to their FDA approval measured their effect on heart attacks, not blood sugar. UAB researchers were surprised when hints of verapamil’s effect were discovered amid their effort to design a drug to shut down a protein called TXNIP.

The team had published several papers over 10 years that describe the way high blood sugar uniquely turns on the gene for TXNIP, and how excessive TXNIP-signaling in diabetes signals cells to self-destruct. Recent studies also have suggested that lowering TXNIP levels in the heart lessens the damage caused by a heart attack.

“We long have felt that finding an oral medication that inhibits beta cell TXNIP expression would represent a major breakthrough, and now we have the first study showing that a drug already proven safe in years of clinical practice may halt the development of diabetes,” said Anath Shalev, M.D., director of the UAB Comprehensive Diabetes Center and senior author of the paper. “Our results are encouraging because patients with diabetes suffer from beta cell death as part of their disease, there has been no treatment targeting this problem and TXNIP-inhibition promises to reverse it.”

Of the nearly 26 million adult patients with diabetes, 67 percent also have high blood pressure.

Based on its findings, the UAB team has redoubled its original effort to design a new class of TXNIP-inhibitors. In partnership with the Southern Research Institute and the Alabama Drug Discovery Alliance, they are now screening a library of 300,000 molecules, a search they hope will yield drug candidates that reverse beta cell death without affecting blood pressure.

In cell studies, the team found that verapamil reduced TXNIP gene expression 50 percent. In diabetic mice, verapamil treatment maintained normal glucose level, while glucose spiked in control mice. This was accompanied by an 80 percent reduction in TXNIP levels in isolated islets of verapamil-treated animals.

Using molecular biology techniques, researchers were able to watch as expression of TXNIP, or thioredoxin-interacting protein, rose in beta cells to abnormal levels as mice became diabetic and then fell again as they received verapamil.

The team also found that treatment only reduced TXNIP gene expression when high blood sugar had driven it to abnormal levels, making the pathway “extremely attractive” as a target for drugs, Shalev said. Future treatments conceivably could return TXNIP levels to normal in diabetic patients, but leave in place the basic level of TXNIP-signaling that cells rely on to regulate life processes. The results also suggest the drug is able to slow diabetes in mice with longstanding disease and is more effective when given early.

“The debate now should begin as to whether physicians should consider verapamil an additional treatment to protect beta cells in patients with both hypertension and diabetes, similar to the use of ACE inhibitors for kidney protection,” said Shalev, who also is a clinician. “As it stands, it can take years before patients with diabetes receive verapamil, possibly missing a window of opportunity. Future clinical studies need to test whether or not earlier treatment could have a profound effect on diabetes progression by saving more beta cells.”

Though no one had previously established the link between calcium channel-blockers, TXNIP and beta cell death, past studies had hinted at a connection. Analysis of the INVEST trial revealed that newly diagnosed diabetes was less common in patients treated with verapamil, especially in the Hispanic population.

In addition to protecting insulin-producing cells, experiments also showed that verapamil countered insulin-resistance that makes the hormone less able to lower blood-sugar levels in diabetic patients. Theory has it that lowering TXNIP levels counters this by increasing glucose uptake in the tissues targeted by insulin (e.g. muscle and fat), a phenomenon observed in mice lacking the TXNIP gene.

Shalev’s team spent years establishing TXNIP as the mandatory link between high blood sugar and beta cell death. The effort reached its first milestone in 2002 in a study that demonstrated the gene for TXNIP had the greatest increase in expression —11-fold greater than any of the 6,000 genes expressed in pancreatic islets — in the face of rising glucose levels. In 2005, the team identified the DNA region that turns on the TXNIP gene in response to high sugar in beta cells and later showed that the carbohydrate response element-binding protein (ChREBP) attaches to DNA there.

Their next paper in 2008 revealed that genetic deletion of TXNIP protects against Type 1 and Type 2 diabetes and too much TXNIP-signaling shuts down the Akt/Bcl-xL pathway that keeps beta cells alive.

TXNIP stands for thioredoxin-interacting protein, and the overactive TXNIP signaling seen in diabetes sharply reduces the antioxidant activity of the protein thioredoxin. The team had found previously that that higher TXNIP levels in the mitochondria of beta cells increase the chances it will pull thioredoxin off of the protein it would otherwise shut down, apoptosis-signaling kinase 1. Once free, this enzyme initiates a chain reaction that ends in beta cell death.

Shalev’s team also has now shown that calcium channel-blockers inhibit signaling through the enzyme calcineurine, which increases ChREBP phosphorylation and keeps it from getting into the beta cell nucleus. With less ChREBP, extra TXNIP gene expression is shut down.

In Shalev’s lab, post-doctoral fellow Guanlan Xu, Ph.D., performed all key cell studies, and research associates Junqin Chen, Ph.D., and Gu Jing, Ph.D., helped with the mouse studies and protein work. The work was supported by Juvenile Diabetes Research Foundation & JNJSI, American Diabetes Association and National Institute of Diabetes, Digestive and Kidney Diseases, part of the National Institutes of Health.

Resistant hypertension affects more than 12 percent of patients who take anti-hypertensive medications to manage the condition. Despite being on three or more medications, these patients have blood pressure that remains high enough to put them at risk for heart attack or stroke. For every 20 point increase in systolic pressure, the risk of cardiovascular episodes doubles, according to The Christ Hospital cardiology researchers.

“Some patients who have resistant hypertension may already be survivors of heart attacks or have undergone surgery, making their blood pressure management that much more critical,” said Eugene Chung, M.D., a lead investigator of the study at The Christ Hospital and medical director of outcomes for the hospital’s Heart and Vascular Center.

In earlier studies, patients who underwent this minimally invasive procedure were able to reduce their pressure by about 30 or so points. The positive earlier trial resultswarranted further study.

The investigational SYMPLICITY™ Renal Denervation System® includes inserting a catheter at the groin and advancing it to the renal arteries where radiofrequency (RF) energy is delivered that disrupts sympathetic nerves around the renal arteries. This prevents neurotransmitters released by these nerves from triggering a hormone response that increases heart rate, constricts blood vessels and raises blood pressure. It is similar to an ablation procedure technique typically used for atrial fibrillation treatment. The application to the sympathetic nerves is novel in the U.S. In earlier SYMPLICITY Phase I and II studies conducted in Europe and Australia, results indicated that the procedure reduced blood pressure significantly.

“Preliminary results suggest that patients need only one such treatment to achieve optimal results, and these results can last for years, significantly decreasing the odds for these higher-risk patients of experiencing a serious heart attack or stroke,” said Dean Kereiakes, M.D., also a lead investigator on the study at The Christ Hospital and medical director of The Christ Hospital Heart and Vascular Center, as well as The Carl and Edyth Lindner Center for Research and Education.

The SYMPLICITY Phase III trial is a prospective, single-blind, randomized, controlled trial that will enroll approximately 530 patients in up to 90 research sites nationwide. Those enrolled will be assigned randomly to either treatment or control groups at a 2:1 ratio. Patients’ blood pressure will be monitored for six months. Researchers will track and report any major adverse events, including death, end-stage renal disease, or organ damage. After six months, patients in the control group will be allowed to receive the RF procedure if deemed clinically necessary.

In the United States alone, it is estimated that one in every three adults, or about 65 million, have high blood pressure, and many more are at risk of developing it.

For more information about SYMPLICITY and enrollment requirements, please contact The Lindner Research Center at 513-585-1777.

Memphis ranked first on the list of the 50 U.S. metropolitan areas that have hypertension risk factors and complications. Furthermore, in 2009, nearly one-third of people in the state of Tennessee had been informed they have high blood pressure, according to the Centers for Disease Control and Prevention. The large-scale Hot Spots analysis, which combined the findings of original research and existing, related research in the field of the study, analyzed data about numerous hypertension risk factors, including mortality related to hypertension – Memphis ranked first nationwide – and obesity; Memphis ranked second highest nationwide.

“Hypertension can lead to a higher risk of serious health consequences like heart attack and stroke if left uncontrolled,” saidPhillip Northcross, M.D., a Memphis-based internal medicine specialist. “The Hot Spots ranking reiterates hypertension’s high prevalence in Memphis and reinforces the importance of patients working with their doctors to lower their blood pressure and reduce their risk for complications.”

The Commit to Control exhibit will visit the Memphis Southern Women’s Show on March 9-11. To motivate residents to control their high blood pressure, the exhibit will offer free blood pressure screenings and the opportunity to see the effects hypertension can have on the body through an animated 3-D simulation. The tour schedule and additional resources on how patients can take steps toward managing their hypertension are available on www.CommitToControl.com. Site visitors can also see a full list of the 50 Hypertension Hot Spots and make an online pledge to talk to their doctors about controlling hypertension. For each pledge made online, Takeda will donate $5, up to $10,000, to Mended Hearts, a community-based, nationwide heart patient support network.

About Hypertension

Hypertension, or high blood pressure, is a chronic medical condition in which the blood pressure is elevated. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure numbers include systolic and diastolic pressures. Systolic pressure is the pressure exerted while the heart is beating. Diastolic blood pressure is the pressure when the heart is at rest. In blood pressure measurements, the systolic number appears above or before the diastolic number. Hypertension is defined as elevated blood pressure about 140 mm Hg or greater systolic or 90 mm Hg or greater diastolic. High blood pressure typically has no symptoms. In fact, of Americans who have hypertension, an estimated 20 percent are still unaware they have it. If left uncontrolled, hypertension can lead to serious health problems, including heart attack, stroke, kidney disease and congestive heart failure. Having high blood pressure can also shorten life expectancy by about five years, unless appropriately treated.

SOURCE Takeda Pharmaceuticals U.S.A., Inc.

African-Americans commonly develop hypertension at a younger age, are less likely to have their blood pressure under control, and disproportionately suffer strokes and fatality when compared with their Caucasian counterparts. Statistics include a 30 percent greater rate of non-fatal stroke, an 80 percent greater rate of fatal stroke, and a staggering 420 percent greater rate of end-stage kidney disease for African-Americans.

But research estimates show that only 51 percent of all patients with hypertension adhere to their medications and that adherence rates are even lower for African-American patients.

Dr. Lewis identified self-efficacy, depression, and patient-provider communication among the factors in medication nonadherence. She called for further study, but advised that these factors are important for healthcare providers to consider when treating hypertensive African-American patients.

“Increasing blood pressure control requires a comprehensive approach,” wrote Dr. Lewis. “Given that self-efficacy and patient-provider communication are modifiable factors, they can be the focus of interventions to increase medication adherence. [Clinicians also] may want to screen their hypertensive patients for depression and treat if necessary.”

Source University of Pennsylvania School of Nursing

Jan A. Staessen, MD, PhD, FESC, FAHA

Studies Coordinating Centre,
Laboratory of Hypertension,
Campus Sint Rafaël,Kapucijnenvoer 35, Block d, Level 00,
B-3000 Leuven, Belgium

What are the main findings of the study?

We analyzed subjects from the population based 11-country IDACO database who had daytime ambulatory blood pressure (ABP) and conventional blood pressure (CBP) measurements.

After excluding persons with diastolic hypertension by CBP (≥90 mmHg) or by daytime ABP (≥85 mmHg), a history of cardiovascular disease, and persons younger than 18 years, our analysis included 7295 persons, of whom 1593 had isolated systolic hypertension.

During a median follow-up of 10.6 years, there were a total of 655 fatal and non-fatal cardiovascular events.  The analyses were stratified by treatment status.  In untreated subjects, those with white coat hypertension (CBP ≥140/<90 mmHg and ABP <135/<85 mmHg) and subjects with normal BP (CBP <140/<90 mmHg and ABP <135/<85 mmHg) were at similar risk (adjusted hazard rate 1.17; 95% confidence interval 0.87-1.57, P=0.29).

Furthermore, in treated subjects with ISH, the cardiovascular risk was similar in elevated conventional and normal daytime systolic BP as compared to those with normal conventional and normal daytime BP (1.10; 0.79-1.53; P=0.57).

However, both treated ISH subjects with white-coat hypertension (2.00; 1.43-2.79; P<0.0001) and treated subjects with normal BP (2.00; 1.58-2.54; P<0.0001) were at higher risk as compared to untreated normotensive subjects.

Were any of the findings unexpected?

Yes.  The finding that treated ISH subjects with white-coat hypertension and treated subjects with normal BP were at higher risk as compared with treated normotensive subjects was unexpected.

What should clinicians and patients take away from this study?

Treated patients with white-coat hypertension or even normotension have a higher risk than truly normotensive untreated subjects.

What recommendations do you have for future research as a result of your study?

White-coat hypertension must probably be redefined taking into account treatment status.

Reference:

Hypertension. 2012 Jan 17. [Epub ahead of print]

Significance of White-Coat Hypertension in Older Persons With Isolated Systolic Hypertension: A Meta-Analysis Using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes Population.

Franklin SS, Thijs L, Hansen TW, Li Y, Boggia J, Kikuya M, Björklund-Bodegård K, Ohkubo T, Jeppesen J, Torp-Pedersen C, Dolan E,Kuznetsova T, Stolarz-Skrzypek K, Tikhonoff V, Malyutina S, Casiglia E, Nikitin Y, Lind L, Sandoya E, Kawecka-Jaszcz K, Imai Y,Wang J, Ibsen H, O’Brien E, Staessen JA; on behalf of the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes Investigators.

Researchers found people who maintained or reduced their blood pressure to normal levels by age 55 had the lowest lifetime risk for CVD (between 22 percent to 41 percent risk). In contrast, those who had already developed high blood pressure by age 55 had a higher lifetime risk (between 42 percent to 69 percent risk).

Using data from 61,585 participants in the Cardiovascular Lifetime Risk Pooling Project, researchers examined how changes in blood pressure during middle age affected lifetime CVD risk. Previous studies had considered a single measurement at a given age. In this study, age 55 was considered a mid-point for middle age.

Starting with baseline blood pressure readings from an average of 14 years prior, researchers tracked blood pressure changes until age 55, then continued to follow the patients until the occurrence of a first cardiovascular event (including heart attack or stroke), death or age 95.

“Taking blood pressure changes into account can provide more accurate estimates for lifetime risk of cardiovascular disease, and it can help us predict individualized risk, and thus, individualized prevention strategies,” said Norrina Allen, Ph.D., lead author of the study and assistant professor in the Department of Preventive Medicine at the Northwestern University Feinberg School of Medicine in Chicago. “Both avoiding hypertension during middle age or delaying the onset of the development of hypertension appear to have a significant impact on an individual’s remaining lifetime risk for CVD.”

Researchers also found:

• Almost 70 percent of all men who develop high blood pressure in middle age will experience a CVD event by 85.
• Women who develop high blood pressure by early middle-age (average age 41) have a higher lifetime risk for CVD (49.4 percent) than those who have maintained normal blood pressure up to age 55.
• Women, in general, had higher increases in blood pressure during middle age.
• At an average age 55, 25.7 percent of men and 40.8 percent of women had normal blood pressure levels; 49.4 percent of men and 47.5 of women had prehypertension.
• The overall lifetime CVD risk for people 55 years or older was 52.5 percent for men and 39.9 percent for women, when factoring in all blood pressure levels.
• The lifetime risk for CVD was higher among Blacks compared with Whites of the same sex, and increased with rising blood pressure at middle age. 

“Since the data suggests that both early elevations and changes over time in blood pressure measurements impact the future risk of CVD, people can take preventive steps early on to reduce their chances of heart attack or stroke,” said Donald M. Lloyd-Jones, M.D., Sc.M., co-author of the study and chair of the Department of Preventive Medicine at the Northwestern University Feinberg School of Medicine. “Maintaining a healthy diet, combined with exercise and weight control, can help reduce blood pressure levels and, consequently, your risk for CVD later in life.”

Co-authors are Jarett D. Berry, M.D., M.S.; Hongyan Ning, M.D., M.S.; Linda Van Horn, Ph.D., R.D.; and Alan Dyer, Ph.D. Author disclosures are on the manuscript.

Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content.

Source: Eurekalert

In 2005, the American Heart Association (AHA) released updated recommendations for blood pressure monitoring, to ensure accurate and consistent blood pressure measurements. Numerous factors including body position, arm position, inter-arm differences, cuff size and cuff placement can affect the reading.

Ray and colleagues compared the blood pressure readings of 40 patients obtained by the traditional method routinely used in clinics, as well as by the AHA-recommended method. Based on these two readings for each patient, the researchers produced two medical profile summaries (one for each technique used), covering past medical history, medication list, drug allergies, vital signs, presence or absence of pain, physical examination and laboratory findings, as well as the last two blood pressure readings. These profiles were reviewed by three physicians who provided hypothetical hypertension treatment recommendations.

Ray and colleagues found that overall, individual blood pressure measurements varied greatly between the two methods. As many as 93 percent of patients had a significant blood pressure difference between the two readings (either over 5 mmHg systolic or over 2 mmHg diastolic), with implications for potential cardiovascular complications.

The researchers observed multiple technical errors during the method that most likely accounted for differences between the blood pressure readings. Out of ten possible errors (as defined by the AHA), the average number of errors per patient during the traditional assessment was four. The most common technical error was the absence of measurements on both arms, presumably to save time during measurement. The time to measure blood pressure using the AHA method was over eight minutes (due to the required five minute resting period between arm measurements) versus two minutes using the traditional method.

According to the hypertension medication treatment decisions provided by the three physicians, 45 percent of patients would have received different treatments based on their two blood pressure measurements.

Ray concludes: “Inaccurate blood pressure assessment is common and may impact hypertension treatment. Clinic staff need to be educated on the AHA recommendations for accurate blood pressure measurement, and encouraged to follow them in order to obtain a more accurate reading. More accurate blood pressure measurement could result in improved hypertension management decisions.”

References
1. Ray GM et al (2011). Blood pressure monitoring technique impacts hypertension treatment. Journal of General Internal Medicine. DOI 10.1007/s11606-011-1937-9
2. The Journal of General Internal Medicine is the official journal of the Society of General Internal Medicine.

Source: Eurekalert