No cardiovascular disease reduction with intensive blood pressure lowering treatment

Blood pressure lowering treatment does not reduce death or cardiovascular disease in healthy individuals with a systolic blood pressure below 140. This is shown in a systematic review and meta-analysis from Umeå University. The results, published in JAMA Internal Medicine, support current guidelines and contradict the findings from the Systolic Blood Pressure Intervention Trial (SPRINT).

Blood pressure treatment goals have been intensively debated since the publication of the SPRINT study in 2015. While current guidelines recommend a systolic blood pressure goal < 140 mm Hg, SPRINT found additional mortality and cardiovascular disease reduction with a goal < 120 mm Hg.

A systematic review and meta-analysis from Umeå University, published today in JAMA Internal Medicine, contradicts these findings. The Umeå study shows that treatment does not affect mortality or cardiovascular events if systolic blood pressure is < 140 mm Hg. The beneficial effect of treatment at low blood pressure levels is limited to trials in people with coronary heart disease.

“Our findings are of great importance to the debate concerning blood pressure treatment goals,” says Dr Mattias Brunström, researcher at the Department of Public Health and Clinical Medicine, Umeå University and lead author.

The study is a meta-analysis, combining data from 74 randomized clinical trials, including more than 300 000 patients. The researchers separated primary preventive studies from studies in people with coronary heart disease or previous stroke. The analysis found that the treatment effect was dependent on how high blood pressure was in previously healthy individuals. If systolic blood pressure was above 140 mm Hg, treatment reduced the risk of death and cardiovascular disease. Below 140 mm Hg, treatment did not affect mortality or the risk of first-ever cardiovascular events.

“Several previous meta-analyses have found that blood pressure lowering treatment is beneficial down to levels below 130 mm Hg. We show that the beneficial effect of treatment at low blood pressure levels is limited to trials in people with coronary heart disease. In primary preventive trials, treatment effect was neutral,” says Mattias Brunström.

Tailoring Nanoparticles to Evade Immune Cells and Prevent Inflammatory Response

A Houston Methodist-led research team showed that the systemic administration of nanoparticles triggers an inflammatory response because of blood components accumulating on their surface. This finding may help researchers create more effective ways to avoid activating the immune system and more precisely direct therapies in patients.

In the journal ACS Nano, the team of nanomedicine and regenerative medicine scientists recently described how specially-engineered nanoparticles (leukosomes) injected into mice can prevent the formation of a layer of biomolecules (protein corona) around their surface. The body’s natural defense response to the formation of this protein is to filter out the foreign objects, in this case the nanoparticles. The presence of immune system regulators, known as macrophage receptors, on the surface of the leukosomes improved the amount of time these nanoparticles remained in the body to reach their target.

Last year, Ennio Tasciotti, Ph.D, senior author and director of the Center for Biomimetic Medicine at Houston Methodist Research Institute and team created these leukosomes and evaluated their ability to treat localized inflammation (May 23, 2016, Nature Materials). Leukosomes are able to target inflamed tissues because their design mimics immune cell membranes.

“Now we have a clearer understanding of how to use our leukosomes to evade those immune cells and prevent the body’s inflammatory response,” Tasciotti said. “We’ve known overactive immune cells can behave like Pac Men, gobbling up the nanoparticles and ridding the body of these ‘foreign invaders’ before they reach the intended target.”

Learning how to treat inflammation by overcoming the body’s own defense mechanisms may lead to broader applications for treating diseases characterized by inflammation such as cancer, cardiovascular and autoimmune diseases.

While the research in ACS Nano helps to improve understanding of the overall properties of leukosomes, further studies are needed to confirm the benefits to patients and ways to prevent the human body from rejecting targeted therapies.

The research was supported by the Italian Ministry of Health, National Institutes of Health and National Cancer Institute, the Department of Defense (BCRP Innovator Expansion), William Randolph Hearst Foundation, and The Cullen Trust for Health Care.

With $8.6 Million Grant From Nih, UCLA-Led Consortium Will Map the Heart’s Nervous System

A consortium directed by UCLA’s Dr. Kalyanam Shivkumar has received a three-year, $8.6 million grant from the National Institutes of Health to map the heart’s nervous system. The group’s goal: To conduct research that leads to new ways to treat cardiovascular disease by targeting nerves in the heart’s nervous system.

More than 800,000 people in the U.S. die each year from cardiovascular diseases such as heart failure, arrhythmia and hypertension. These problems often are linked to the autonomic nervous system, the part of the nervous system that signals the heart to beat and controls breathing, digestion and other body processes that typically happen without conscious effort.

Researchers believe that modulating those electrical signals holds promise as a way to treat heart failure and other common cardiovascular problems.

“Understanding the nervous system’s control of the heart is such a complex problem that it requires a collaborative approach, and we’re pleased that so many experts are coming together for this initiative,” said Shivkumar, the study’s lead investigator and director of the UCLA Cardiac Arrhythmia Center and Electrophysiology Programs.

“Our goal is to precisely map the heart’s anatomy and code the function of the nerves that control the heart from a very basic level all the way to clinical studies in humans.”

UCLA is one of seven institutions participating in the project. Principal investigators at the other universities are Dr. Viviana Gradinaru of Caltech, Dr. Stephen Liberles of Harvard University, Dr. Charless Fowlkes of UC Irvine, Dr. Irving Zucker of the University of Nebraska Medical Center, Dr. Beth Habecker of Oregon Health and Science University and Dr. David Paterson of Oxford University.

The information the consortium produces could point the way to new therapies that target neural structures, and it could suggest ways for scientists to create more effective electrical stimulation therapies based on the methods being used today, said Shivkumar, who is also chief of the UCLA Cardiovascular Interventional programs and a professor of medicine, radiology and bioengineering at the David Geffen School of Medicine at UCLA.

“Understanding how the nervous system controls the heart offers researchers a tremendous opportunity to open up new paths to treat cardiac disease,” said Dr. Kelsey Martin, dean of the David Geffen School of Medicine. “We are thrilled that our UCLA team is leading the charge on this exciting new research.”

The award is from an NIH program called Stimulating Peripheral Activity to Relieve Conditions, or SPARC, which supports research on how the electrical signals of the peripheral nerves that connect the brain and spinal cord to the rest of the body control internal organ function. The UCLA-led consortium is one of 27 multidisciplinary research teams that received SPARC awards in 2016; the grants totaled more than $20 million.

Scientists Find Culprit Responsible For Calcified Blood Vessels In Kidney Disease

Scientists have implicated a type of stem cell in the calcification of blood vessels that is common in patients with chronic kidney disease. The research will guide future studies into ways to block minerals from building up inside blood vessels and exacerbating atherosclerosis, the hardening of the arteries.

The study, led by researchers at Washington University School of Medicine in St. Louis, appears Sept. 8 in the journal Cell Stem Cell.

“In the past, this calcification process was viewed as passive — just mineral deposits that stick to the walls of vessels, like minerals sticking to the walls of water pipes,” said senior author Benjamin D. Humphreys, MD, PhD, director of the Division of Nephrology and an associate professor of medicine. “More recently, we’ve learned that calcification is an active process directed by cells. But there has been a lot of controversy over which cells are responsible and where they come from.”

The cells implicated in clogging up blood vessels with mineral deposits live in the outer layer of arteries and are called Gli1 positive stem cells, according to the study. Because they are adult stem cells, Gli1 cells have the potential to become different types of connective tissues, including smooth muscle, fat and bone.

Humphreys and his colleagues showed that in healthy conditions, Gli1 cells play an important role in healing damaged blood vessels by becoming new smooth muscle cells, which give arteries their ability to contract. But with chronic kidney disease, these cells likely receive confusing signals and instead become a type of bone-building cell called an osteoblast, which is responsible for depositing calcium.

“We expect to find osteoblasts in bone, not blood vessels,” Humphreys said. “In the mice with chronic kidney disease, Gli1 cells end up resembling osteoblasts, secreting bone in the vessel wall. During kidney failure, blood pressure is high and toxins build up in the blood, promoting inflammation. These cells may be trying to perform their healing role in responding to injury signals, but the toxic, inflammatory environment somehow misguides them into the wrong cell type.”

The researchers also studied donated tissue from patients who died of kidney failure and who showed calcification in the aorta, the body’s largest artery.

“We found Gli1 cells in the the calcified aortas of patients in exactly the same place we see these cells in the mice,” Humphreys said. “This is evidence that the mice are an accurate model of the disease in people.”

About 20 million adults in the U.S. have some degree of chronic kidney disease, according to the Centers for Disease Control and Prevention. But most of these patients never develop late-stage kidney failure that requires dialysis or kidney transplantation because they succumb to cardiovascular disease first, Humphreys said. The buildup of plaque in the arteries that is characteristic of cardiovascular disease is worsened in patients with diseased kidneys because of the additional mineral deposits.

Further supporting the argument that Gli1 cells are driving the calcification process, Humphreys and his colleagues showed that removing these cells from adult mice prevented the formation of calcium in their blood vessels.

“Now that we have identified Gli1 cells as responsible for depositing calcium in the arteries, we can begin testing ways to block this process,” Humphreys said. “A drug that works against these cells could be a new therapeutic way to treat vascular calcification, a major killer of patients with kidney disease. But we have to be careful because we believe these cells also play a role in healing injured smooth muscle in blood vessels, which we don’t want to interfere with.”

Humphreys is continuing to focus on the kidney in studying ways to guide Gli1 cells away from bone-building osteoblasts and toward vessel-healing smooth muscle cells. The study’s first author, Rafael Kramann, MD, a former postdoctoral researcher in Humphreys’ lab and who is now at Aachen University in Germany, is studying the same process with a focus on the heart.