Novel blood test helps evaluate severity in pulmonary arterial hypertension, a rare lung disease

Researchers at the National Institutes of Health have found that a novel blood test can be used to easily evaluate disease severity in patients with pulmonary arterial hypertension (PAH) and predict survivability. PAH is a rare, life-threatening condition that causes unexplained high blood pressure in the lungs. In early clinical studies, the researchers showed the test to significantly improve upon conventional tests, some of which use invasive tools.

Computed tomography 3D surface rendering of the lungs and heart from a patient with pulmonary arterial hypertension demonstrating trachea and major airways (yellow), an enlarged heart (red), enlarged main pulmonary artery (large blue vessel on top of heart) and thinning of the peripheral pulmonary vessels (blue). Marcus Y. Chen, M.D., NHLBI

The new blood test measures DNA fragments shed by damaged cells. Researchers found that these fragments, called cell-free DNA, were elevated in the blood of patients with PAH and increase with disease severity. If future studies confirm the findings, this first-of-its-kind blood test for PAH patients could allow doctors to intervene faster to prevent or delay progression of the disease and possibly save lives. Cell-free DNA is a relatively new analytical technique that is growing in its potential medical uses, which include the early detection of heart- and lung-transplant rejection as well as early detection of cancer.  

The study was funded by the National Heart, Lung, and Blood Institute (NHLBI) and the NIH Clinical Center, both part of NIH. The findings will appear online in the journal Circulation, a publication of the American Heart Association.

PAH is a rare form of pulmonary hypertension that can cause difficulty breathing, chest pain, and fatigue. The disease, whose exact cause is unknown, is estimated to affect less than 50,000 people in the United States, according to the NIH’s Genetic and Rare Diseases Information Center. It is characterized by progressive narrowing and blockage of the small pulmonary arteries of the lungs, strain on the right side of the heart, and eventual death from heart failure. The damage to the lung in severe cases can require lung transplantation. Patients with PAH have a high death rate, and the condition mostly affects women. Despite treatment advances, it currently has no cure.

Current tests used to monitor PAH severity rely on established risk prediction scores based on clinical symptoms and on the use of an invasive catheter to measure pressure in the lungs. Doctors sometimes use echocardiography, or heart imaging, to measure pressures in the heart as an indirect measurement of lung pressure, but these tests tend to lack reliability and sensitivity.

“Researchers have been actively searching for novel, less-invasive approaches to evaluate PAH severity, disease progression, and response to therapy for more than a decade. These cell-free DNA analyses represent progress toward that goal,” said study co-author Michael A. Solomon, M.D., M.B.A., who is part of the NHLBI Cardiovascular Branch and co-director of the NIH Clinical Center Pulmonary Arterial Hypertension Section.

Sean Agbor-Enoh, M.D., Ph.D., study co-author and chief of the NHLBI’s Laboratory of Applied Precision Omics, agreed. “Here we’re proposing a one-time test where you collect a vial of blood from a patient and use that to predict survival. We’re very encouraged by the early results.”

 In the current study, the research team analyzed cell-free DNA from blood samples taken from 209 adult patients, predominately women, diagnosed with PAH at two large U.S. medical centers. The researchers compared the results to cell-free DNA measured from a control group of 48 healthy volunteers without PAH at the NIH Clinical Center. 

They found that cell-free DNA was elevated in patients with PAH, and also found that cell-free DNA concentrations increased in proportion to the severity of the disease. Patients with the highest level of cell-free DNA had a 3.8 times greater risk of either death or a need for lung transplantation compared to those with the lowest level of cell-free DNA, the researchers said.

Further analyses of cell-free DNA samples revealed that multiple tissue types – including the heart, blood vessels, fat tissue, and inflammatory cells circulating in the blood – were affected by PAH. The new blood test will allow researchers to better pinpoint the specific tissues involved in the PAH disease process. This knowledge may lead to new drug interventions for PAH, whose current treatment options may slow but not halt or reverse disease progression.

In addition to funding from the Intramural Research Program of the NHLBI, this research is supported by the NIH Clinical Center Research Award for Staff Clinicians Program, the NIH Distinguished Scholar Award, the Lasker Clinical Research Scholars Program, and the Intramural Research Programs of the NIH Clinical Center. 

More than 700 million people with untreated hypertension

The number of adults aged 30–79 years with hypertension has increased from 650 million to 1.28 billion in the last thirty years, according to the first comprehensive global analysis of trends in hypertension prevalence, detection, treatment and control, led by Imperial College London and WHO, and published in The Lancet. Nearly half these people did not know they had hypertension.

Hypertension significantly increases the risk of heart, brain and kidney diseases, and is one of the top causes of death and disease throughout the world. It can be easily detected through measuring blood pressure, at home or in a health centre, and can often be treated effectively with medications that are low cost.

The study, conducted by a global network of physicians and researchers, covered the period 1990–2019. It used blood pressure measurement and treatment data from over 100 million people aged 30–79 years in 184 countries, together covering 99% of the global population, which makes it the most comprehensive review of global trends in hypertension to date.

By analysing this massive amount of data, the researchers found that there was little change in the overall rate of hypertension in the world from 1990 to 2019, but the burden has shifted from wealthy nations to low- and middle-income countries. The rate of hypertension has decreased in wealthy countries – which now typically have some of the lowest rates – but has increased in many low- or middle-income countries.

As a result, Canada, Peru and Switzerland had among the lowest prevalence of hypertension in the world in 2019, while some of the highest rates were seen in the Dominican Republic, Jamaica and Paraguay for women and Hungary, Paraguay and Poland for men. (See notes to editors for country breakdowns/rankings).

According to the WHO, although the percent of people who have hypertension has changed little since 1990, the number of people with hypertension doubled to 1.28 billion. This was primarily due to population growth and ageing. In 2019, over one billion people with hypertension (82% of all people with hypertension in the world) lived in low- and middle-income countries.

Pregnancy hypertension risk increased by traffic-related air pollution

A new report from the National Toxicology Program (NTP) suggests that traffic-related air pollution increases a pregnant woman’s risk for dangerous increases in blood pressure, known as hypertension.

NTP scientists evaluated published research on the link between traffic-related air pollution, or TRAP, and hypertensive disorders broken down by pollutant measurements of TRAP, such as particulate matter (PM2.5). PM is the term for a mixture of solid particles and liquid droplets found in the air, and PM2.5 refers to fine inhalable particles, with diameters that are generally 2.5 micrometers or smaller. The average human hair is about 70 micrometers in diameter, about 30 times larger than the largest fine particle.

“What we found when we reviewed the literature is that exposure to PM2.5 from traffic emissions was associated with development of hypertensive disorders in pregnant women,” said Brandy Beverly, Ph.D., lead scientist and researcher at the National Institute of Environmental Health Sciences, part of the National Institutes of Health. “When these women are exposed to PM2.5 during their entire pregnancy, the likelihood of developing preeclampsia increases by about 50%.”

Other components of TRAP that NTP evaluated included nitrogen oxides, carbon monoxide, black carbon, and elemental carbon, along with parameters like traffic density and mothers’ proximity to main roads.

For example, the literature suggests that women who live within a quarter of a mile of a major roadway or in high traffic density regions may be at an increased risk for developing hypertensive disorders of pregnancy.

TRAP comes from the combustion of fossil fuels by motor vehicles. These vehicle emissions are mixtures of gases and particles that are easily inhaled and have adverse health effects. TRAP is known to be a major risk factor for cardiovascular disease, including hypertension.

Hypertensive disorders of pregnancy complicate more than 10% of pregnancies worldwide and are a leading cause of maternal and fetal illness and death. According to the American College of Obstetrics and Gynecology, mothers with hypertension during pregnancy are more likely to have a pre-term delivery. Their infants are at greater risk for low birthweight and a range of long-term health problems associated with pre-mature birth.

“Hypertensive disorders of pregnancy refer to a range of clinical conditions, all of which include high blood pressure during pregnancy,” said Beverly. “The disorders are classified into four distinct types, based on differences in the timing and onset of the symptoms.”

Study links irregular sleep patterns to metabolic disorders

A new study has found that not sticking to a regular bedtime and wakeup schedule, and getting different amounts of sleep each night, can put a person at higher risk for obesity, high cholesterol, hypertension, high blood sugar and other metabolic disorders. In fact, for every hour of variability in time to bed and time asleep, a person may have up to a 27% greater chance of experiencing a metabolic abnormality.

The results of the study, which was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appear today in the journal Diabetes Care(link is external).

“Many previous studies have shown the link between insufficient sleep and higher risk of obesity, diabetes, and other metabolic disorders,” said study author Tianyi Huang, Sc.D., epidemiologist of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston. “But we didn’t know much about the impact of irregular sleep, high day-to-day variability in sleep duration and timing. Our research shows that, even after considering the amount of sleep a person gets and other lifestyle factors, every one-hour night-to-night difference in the time to bed or the duration of a night’s sleep multiplies the adverse metabolic effect.”

For the current study, researchers followed 2,003 men and women, ages 45 to 84, participating in the NHLBI-funded Multi-Ethnic Study of Atherosclerosis (MESA). The participants were studied for a median of six years to find out the associations between sleep regularity and metabolic abnormalities. To ensure objective measurement of sleep duration and quality, participants wore actigraph wrist watches to closely track sleep schedules for seven consecutive days. They also kept a sleep diary and responded to standard questionnaires about sleep habits and other lifestyle and health factors. Participants completed the actigraphy tracking between 2010 and 2013 and were followed until 2016 and 2017.

“Objective metrics and a big and diverse sample size are strengths of this study,” said Michael Twery, Ph.D., director of the NHLBI’s National Center on Sleep Disorders Research. “As is the study’s ability to look not only at current factors, but to conduct a prospective analysis that allowed us to assess whether patterns of irregular sleep could be linked to future metabolic abnormalities.”

The researchers’ hypothesis that there were, in fact, such associations, proved correct. Individuals with greater variations in their bedtimes and in the hours they slept had a higher prevalence of metabolic problems, and these associations persisted after adjusting for average sleep duration. This was also the case when they looked at the participants who developed metabolic disorders during the 6.3 years of follow up.

The prospective results showed that the variations in sleep duration and bedtimes preceded the development of metabolic dysfunction. According to the authors, this provides some evidence supporting a causal link between irregular sleep and metabolic dysfunction.

Participants whose sleep duration varied more than one hour were more likely to be African-Americans, work non-day shift schedules, smoke, and have shorter sleep duration. They also had higher depressive symptoms, total caloric intake, and index of sleep apnea.

Increasing sleep duration or bedtime variability was strongly associated with multiple metabolic and simultaneous problems such as lower HDL cholesterol and higher waist circumference, blood pressure, total triglycerides, and fasting glucose.

“Our results suggest that maintaining a regular sleep schedule has beneficial metabolic effects,” said study coauthor Susan Redline, M.D., senior physician in the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital. “This message may enrich current prevention strategies for metabolic disease that primarily focus on promoting sufficient sleep and other healthy lifestyles.” 

Diet rich in fried and processed foods linked to increased hypertension in black Americans

NIH-funded study suggests a change in diet could mitigate increased risk for stroke.

New findings suggest that diet is a major contributor for the increased risk of hypertension in black compared to white Americans.

Diet rich in fried and processed foods blamed for black Americans’ health problems. Photo credit: Medical Xpress

The results, published in the Journal of the American Medical Association, are part of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, which looks at the incidence of stroke in approximately 30,000 individuals. The study is funded by the National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health.

“This study addresses a lead cause of racial disparity in mortality and identifies potential lifestyle changes that could reduce racial disparities in both stroke and heart disease,” said Claudia Moy, Ph.D., NINDS program director and one of the study authors.

In the study, led by George Howard, Dr.P.H., a biostatistics professor at the University of Alabama at Birmingham, researchers studied individuals over the age of 45 over a period of 10 years and looked to identify risk factors associated with the higher likelihood of developing high blood pressure in the study participants.

“The majority of disparities we see in the health of black versus white Americans are cardiovascular in nature,” said Dr. Howard, “and of these, all are tied to an increase in high blood pressure.”

For both men and women, a diet composed of high amounts of fried and processed foods and sweetened beverages was the greatest factor associated with why blacks are at a greater risk of developing high blood pressure compared to whites. For both men and women, other important factors included salt intake and education level.  For women, additional factors contributing to the racial difference in high blood pressure included obesity and waist size.

“One of the main factors affecting the difference between the black and white population is cardiovascular disease, and the increased risk of high blood pressure among black Americans could help explain why their life expectancy is four years shorter than that of whites,” said Dr. Howard. “Understanding how we can prevent this increased risk of hypertension in blacks is critical for reducing health disparities among the black population.”

The researchers hope that these findings could be applied to reduce the prevalence of hypertension and thus the risk of stroke and heart attack in the black American population. This study suggests that lifestyle changes, particularly changes in diet, could help reduce the disparities seen in black versus white Americans.

“The best way to treat high blood pressure is to prevent it from occurring in the first place,” said Dr. Howard.

The REGARDS study includes more than 30,000 black and white Americans, approximately half of whom live in the Stroke Belt, an area in the southeastern United States where the rate of stroke mortality is higher than the rest of the country. Of these, 6,897 participants, 1,807 black and 5,090 white, were analyzed for this study.

In 2016, the NINDS launched a stroke prevention campaign called Mind Your Risks, which is designed to educate people aged 45-65 about the link between uncontrolled high blood pressure and the risk of having a stroke or developing dementia later in life.

DASH ranked Best Diet Overall for eighth year in a row by U.S. News and World Report

For the eighth consecutive year, U.S. News and World Report ranked the National Institutes of Health-developed DASH Diet “best overall” diet among nearly 40 it reviewed. The announcement came just as new research suggests that combining DASH, or Dietary Approaches to Stop Hypertension, with a low-sodium diet has the potential to lower blood pressure as well as or better than many anti-hypertension medications.

Empanadas are a great staple of Latino cuisine. Empanapitas, a new take with pita bread, are a DASH healthier, but just as tasty.NHLBI

With its focus on vegetables, fruits, whole grains, low-fat dairy, and lean proteins, DASH,  tied this year for “best overall” diet and was ranked No. 1 in the “healthy eating” and “heart disease prevention” categories.

According to the World Health Organization, hypertension, more commonly referred to as high blood pressure, is the most common chronic condition worldwide. It is a major risk factor for heart disease, affects 1 billion people, and accounts for 1 in 8 deaths each year.

Researchers funded by NIH’s National Heart, Lung, and Blood Institute (NHLBI) developed DASH to prevent and treat high blood pressure, but the diet also has proven highly effective in lowering blood cholesterol.

“The consistent high rankings of DASH over the years bode well for the way the diet is received and adopted, not just by health professionals, but by the public at large,” said Janet de Jesus, M.S., registered dietitian and program officer at NHLBI’s Center for Translation Research and Implementation Science. “This is especially gratifying now that new research underscores the significant blood-pressure lowering effects of a reduced intake of sodium in combination with the DASH diet.”

Previous research has shown that people who follow the DASH diet may be able to reduce their blood pressure by a few points in just two weeks. Over time, their systolic blood pressure (the top number in a blood pressure reading) could drop by eight to 14 points, which significantly reduces the risk of cardiovascular disease.

The positive health effects could be even greater if DASH is combined with a low sodium diet. An NHLBI-funded study(link is external) of more than 400 adults with prehypertension, or stage 1 high blood pressure, found that the combination of a low-salt diet with DASH substantially lowers systolic blood pressure. The results were impressive, according to de Jesus. Overall, participants who started out with the highest blood pressure achieved the greatest reductions.

“An interesting aspect of the DASH diet is that the effects are greater in people with hypertension or higher blood pressure at baseline, which is comparable to anti-hypertensive medications,” said Stephen Juraschek, M.D., an adjunct assistant professor at Johns Hopkins University, Baltimore, and an instructor of medicine at Harvard Medical School, Boston, and the study’s first author. “Our results add to the evidence that dietary interventions can be as effective as – or more effective than – antihypertensive drugs in those at highest risk for high blood pressure, and should be a routine first-line treatment option for such individuals.”

DASH is not a fad diet, but a healthy eating plan that supports long-term lifestyle changes. It is low in saturated fat, trans fat, and cholesterol. It emphasizes fruits, vegetables, and low-fat dairy foods, and includes whole grains, poultry, fish, lean meats, beans, and nuts. It is rich in potassium, calcium, and magnesium, as well as protein and fiber. However, it calls for a reduction in high fat red meat, sweets, and sugary beverages.

The DASH diet was one of 38 diets reviewed and scored by the U.S. News and World Report’s panel of health experts. To receive top ratings a diet must be relatively easy to follow, nutritious, safe, effective for weight loss and protective against diabetes and heart disease.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at https://www.nhlbi.nih.gov.