Fathers' age, lifestyle associated with birth defects

A growing body of research is revealing associations between birth defects and a father's age, alcohol use and environmental factors, say researchers at Georgetown University Medical Center. They say these defects result from epigenetic alterations that can potentially affect multiple generations.

The study, published in the American Journal of Stem Cells, suggest both parents contribute to the health status of their offspring -- a common sense conclusion which science is only now beginning to demonstrate, says the study's senior investigator, Joanna Kitlinska, PhD, an associate professor in biochemistry, and molecular and cellular biology.

"We know the nutritional, hormonal and psychological environment provided by the mother permanently alters organ structure, cellular response and gene expression in her offspring," she says.

"But our study shows the same thing to be true with fathers -- his lifestyle, and how old he is, can be reflected in molecules that control gene function," she says. "In this way, a father can affect not only his immediate offspring, but future generations as well."

For example, a newborn can be diagnosed with fetal alcohol spectrum disorder (FASD), even though the mother has never consumed alcohol, Kitlinska says. "Up to 75 percent of children with FASD have biological fathers who are alcoholics, suggesting that preconceptual paternal alcohol consumption negatively impacts their offspring."

The report is a review of evidence, human and animal, published to date on the link between fathers and heritable epigenetic programming.

Among the studies reviewed are ones that find:

• Advanced age of a father is correlated with elevated rates of schizophrenia, autism, and birth defects in his children;
• A limited diet during a father's pre-adolescence has been linked to reduced risk of cardiovascular death in his children and grandchildren;
• Paternal obesity is linked to enlarged fat cells, changes in metabolic regulation, diabetes, obesity and development of brain cancer;
• Psychosocial stress on the father is linked to defective behavioral traits in his offspring; and
• Paternal alcohol use leads to decreased newborn birth weight, marked reduction in overall brain size and impaired cognitive function.

"This new field of inherited paternal epigenetics needs to be organized into clinically applicable recommendations and lifestyle alternations," Kitlinska says. "And to really understand the epigenetic influences of a child, we need to study the interplay between maternal and paternal effects, as opposed to considering each in isolation."

Lowering target blood pressure would save lives and money

Lowering blood pressure goals for adults at high risk of cardiovascular disease could save tens of thousands of lives annually and reduce costs, according to a computer simulation by researchers at Columbia University Medical Center (CUMC) and NewYork-Presbyterian. Results of the study, published today in the online edition of Hypertension and presented today at the American Society of Hypertension Annual Scientific Meeting, could prompt a revision of national hypertension treatment guidelines, which had relaxed blood pressure goals for specific high-risk patients in recent years.

The results complement recent evidence from the Systolic Blood Pressure Intervention Trial (SPRINT), which found that having a more intensive systolic blood pressure (SBP) goal of 120 mmHg in patients at high risk for cardiovascular disease reduced both cardiovascular events and mortality by about one quarter, compared with the current goal of 140 mmHg.

In 2014, the 8th Joint National Committee (JNC8) on Detection, Evaluation, and Treatment of High Blood Pressure--appointed by the National Heart, Lung, and Blood Institute -- issued new guidelines recommending that physicians aim for an SBP of 140 mmHg in adults with diabetes and/or chronic kidney disease and 150 mmHg in healthy adults over age 60. The new guidelines represented a major departure from previous JNC7 guidelines recommending SBPs of 130 mmHg and 140, mmHg for these groups, respectively, and were not endorsed by either the American Heart Association or the American College of Cardiology. Under the 2014 guidelines, over 5 million fewer individuals annually would receive drug treatment to lower their blood pressure, compared with the prior 2003 guidelines.

The CUMC team conducted a computer simulation to determine the value of adding the lower, life-saving SBP goal identified in SPRINT to the JNC7 and JNC8 guidelines for high-risk patients between the ages of 35 and 74 years. (High risk was defined as existing cardiovascular disease, chronic kidney disease, or a 10-year cardiovascular disease risk greater than 15 percent in patients older than 50 years and with a pre-treatment SBP greater than 130 mmHg.) The researchers performed the simulation on data from a national population of adults and added data on the quality-of-life impact of side effects as well as drug and blood pressure monitoring costs.

The study found that lowering treatment goals for this population in the JNC8 guidelines would prevent up to 43,000 additional deaths from cardiovascular disease each year. Adding more intensive goals to the JNC7 guidelines would prevent an additional 35,000 deaths.

The study also revealed that adding the lower SBP goals to the JNC7 and JNC8 guidelines would decrease overall treatment costs for men and would be cost-effective (representing a good value) compared with standard treatment in women.

"Hypertension treatment is cheap and effective, and fear of side effects should not dissuade physicians from treating to lower goals in high-risk individuals under 75 years of age," said Nathalie Moise, MD, MS, lead author, assistant professor of medicine at CUMC and faculty member of the Center for Behavioral Cardiovascular Health.

Any future savings would be sensitive to higher drug costs, added Dr. Moise. "Containing drug costs will be integral to affordable implementation of intensive blood pressure goals in this high-risk group."

"Our simulation shows that we have everything to gain by taking a more aggressive approach to lowering systolic blood pressure in patients with certain cardiovascular disease risk factors," concluded Dr. Andrew Moran, MD, MPH, the Herbert Irving Assistant Professor of Medicine at CUMC and physician at NewYork-Presbyterian/Columbia.

Being fit may slow lung function decline as we age

Being fit may reduce the decline in lung function that occurs as we grow older, according to research presented at the ATS 2016 International Conference.

"While everyone's lung function declines with age, the actual trajectory of this decline varies among individuals, " said Lillian Benck, MD, a medical resident at Northwestern University Feinberg School of Medicine, Chicago, Illinois, and study lead investigator. "What is less known is, beyond smoking, what factors affect this rate of decline."

Dr. Benck added that even though the majority of people will not develop lung disease in their lifetime, "declining lung function is known to increase overall morbidity and mortality even in the absence of overt pulmonary disease."

Dr. Benck and her colleagues analyzed data from the National Heart, Lung, and Blood Institute's CARDIA (Coronary Risk Development in Young Adults Study), which began in 1985-86 with 5,115 healthy black and white men and women, aged 18-30. The study has measured participant's cardiopulmonary fitness periodically over 20 years using a graded treadmill test. At the beginning of the study and at each follow-up assessment, pulmonary function (PF) was also assessed by measuring forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).

After adjusting for age, smoking, body mass index and change in BMI, the association between fitness and lung function remained statistically significant.

Researchers found that participants:

• in the top quartile of baseline fitness experienced the least annual decline in PF.
• with the greatest decline in fitness experienced the greatest decline in FEV1and PF over 20 years.
• with sustained or improved fitness experienced the least decline in PF over 20 years.

Dr. Benck said that the last finding is noteworthy because it indicates that fitness matters, not just at a single point in time but over many years. "Fitness early in life and at middle age appears to attenuate this natural decline," she said, noting that the benefit of fitness was even seen among smokers.

Because it is an observational study, researchers cannot claim cause and effect. However, they noted several important strengths, including a large study population and long-term follow-up and objective measurements of fitness and lung health.

Dr. Benck said that CARDIA will continue to follow participants and may eventually provide insights into whether fitness not only preserves lung function, but also reduces the risk of developing lung disease.

Nearly half of all heart attacks may be 'silent'

Nearly half of all heart attacks may be silent and like those that cause chest pain or other warning signs, silent heart attacks increase the risk of dying from heart disease and other causes, according to new research in the American Heart Association's journal Circulation.

A heart attack does not always have classic symptoms, such as pain in your chest, shortness of breath and cold sweats. In fact, a heart attack can occur without symptoms and it is called a silent heart attack (blood flow to the heart muscle is severely reduced or cut off completely).

"The outcome of a silent heart attack is as bad as a heart attack that is recognized while it is happening," said Elsayed Z. Soliman, M.D., MSc., M.S., study senior author and director of the epidemiological cardiology research center at Wake Forest Baptist Medical Center, Winston-Salem, North Carolina. "And because patients don't know they have had a silent heart attack, they may not receive the treatment they need to prevent another one."

Researchers analyzed the records of 9,498 middle-age adults already enrolled in the Atherosclerosis Risk in Communities (ARIC), a study analyzing the causes and outcomes of atherosclerosis - hardening of the arteries. Researchers examined heart attack differences between blacks and whites as well as men and women. Over an average of nine years after the start of the study, 317 participants had silent heart attacks while 386 had heart attacks with clinical symptoms. Researchers continued to follow participants for more than two decades to track deaths from heart attack and other diseases.

They found that silent heart attacks:

• made up 45 percent of all heart attacks; increased the chances of dying from heart disease by 3 times; 
• increased the chances of dying from all causes by 34 percent; and 
• were more common in men but more likely to cause death in women.

"Women with a silent heart attack appear to fare worse than men," Soliman said. "Our study also suggests that blacks may fare worse than whites, but the number of blacks may have been too small to say that with certainty."

Researchers accounted for many factors that could bias results, including smoking, body weight, diabetes, high blood pressure and cholesterol. They did not adjust for access to care but did adjust for income and education, which could impact access to care.

Symptoms of silent heart attacks appear so mild that they are barely noticed, if at all. They are detected later, usually when patients undergo an electrocardiogram, better known as an ECG or EKG, to check their heart's electrical activity, researchers said.

Soliman said that silent heart attacks, once discovered, should be treated as aggressively as heart attacks with symptoms.

"The modifiable risk factors are the same for both kinds of heart attacks," he said. "Doctors need to help patients who have had a silent heart attack quit smoking, reduce their weight, control cholesterol and blood pressure and get more exercise."

In 1987, the ARIC Study began enrolling participants who were free of heart disease in four U.S. communities in Maryland, Minnesota, Mississippi and North Carolina to determine the risk factors for heart disease and health effects of hardening of the arteries over time.

NEW PERSPECTIVES ON HOW TO DEFINE THE HEALTH AND WELL-BEING OF AGING AMERICANS

Chronological age itself plays almost no role in accounting for differences in older people's health and well-being, according to a new, large-scale study by a multidisciplinary team of researchers at the University of Chicago.

The work, part of the National Social Life, Health, and Aging Project (NSHAP), supported by the National Institute on Aging of the National Institutes of Health, is a major longitudinal survey of a representative sample of 3,000 people aged 57 to 85 done by the independent research organization NORC at UChicago. The study yielded comprehensive new data about the experience of aging in America that formed the underpinning of the research and its conclusions.

The research presents a sharp departure from the traditional biomedical model's reliance on a checklist of infirmities centered on heart disease, cancer, diabetes, high blood pressure, and cholesterol levels.

Using what they call a "comprehensive model" of health and aging, the team has shown how other factors such psychological well-being, sensory function, mobility and health behaviors are essential parts of an overall health profile that better predicts mortality.

"The new comprehensive model of health identifies constellations of health completely hidden by the medical model and reclassifies about half of the people seen as healthy as having significant vulnerabilities that affect the chances that they may die or become incapacitated within five years," said UChicago biopsychologist Martha McClintock, lead author of "An Empirical Redefinition of Comprehensive Health and Well-being in the Older Adults of the U.S.," in the current issue of the Proceedings of the National Academy of Sciences.

"At the same time, some people with chronic disease are revealed as having many strengths that lead to their reclassification as quite healthy, with low risks of death and incapacity," co-author and demographer Linda Waite added.

The paper is based on the results of a major longitudinal study of aging Americans, funded by the National Institute on Aging, that is the first of its kind to collect this sort of information from a scientifically selected group of people.

The comprehensive model reflects a definition of health long advanced, but little studied, by the World Health Organization that considers health to include psychological, social, and physical factors in addition to the diseases that are the basis for the current medical model of health.

McClintock is the David Lee Shillinglaw Distinguished Service Professor in Psychology. Waite is the Lucy Flower Professor in Sociology. Other members of the team are geriatrician William Dale, associate professor of medicine, and chief, Section of Geriatrics & Palliative Medicine at UChicago Medicine; and sociologist Edward Laumann, the George Herbert Mead Distinguished Service Professor in Sociology.

In addition to finding that chronological age itself plays little or no role in determining differences in health, the research also found that:

Cancer by itself is not related to other conditions that undermine health.
Poor mental health, which afflicts one in eight older adults, undermines health in ways not previously recognized.
Obesity seems to pose little risk to older adults with excellent physical and mental health.
Sensory function and social participation play critical roles in sustaining or undermining health.
Having broken a bone since age 45 is a major marker for future health issues in people's lives.
Older men and women have different patterns of health and well-being during aging.
Mobility is one of the best markers of well-being.
Six new ways of looking at aging

The comprehensive model's healthiest category represented 22 percent of older Americans. This group was typified by higher obesity and blood pressure, but had fewer organ system diseases, better mobility, sensory function, and psychological health. They had the lowest prevalence of dying or becoming incapacitated (six percent) five years into the study.

A second category had normal weight, low prevalence of cardiovascular disease and diabetes, but had one minor disease such as thyroid disease, peptic ulcers, or anemia and were twice as likely to have died or become incapacitated within five years. Two emerging vulnerable classes of health traits, completely overlooked by the medical model, included 28 percent of the older population. One group included people who had broken a bone after age 45. A second new class had mental health problems, in addition to poor sleep patterns, engaged in heavy drinking, had a poor sense of smell and walked slowly, all of which correlate with depression.

The most vulnerable older people were in two classes, one characterized by immobility and uncontrolled diabetes and hypertension. A majority of people in each of these categories were women, who tend to outlive men.

"From a health system perspective, a shift of attention is needed from disease-focused management, such as medications for hypertension or high cholesterol, to overall well-being across many areas," said Dale.

"Instead of policies focused on reducing obesity as a much lamented health condition, greater support for reducing loneliness among isolated older adults or restoring sensory functions would be more effective in enhancing health and well-being in the older population," said Laumann.

Higher levels of fitness reduce the risk of developing of diabetes and prediabetes

A new study analysing fitness levels across two decades is the longest study demonstrating that higher levels of cardiorespiratory fitness (CRF) reduce the risk for developing prediabetes or diabetes. The study, which adjusts for changes in body mass index over time, provides strong evidence supporting the commonly accepted dogma that fitness is beneficial in reducing the risk for prediabetes/diabetes. The research is published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) by Dr Lisa Chow, University of Minnesota, Minnesota, USA, and colleagues.

A number of previous studies have shown people who maintain or increase their CRF through adulthood have a lower risk of developing diabetes, abnormal metabolic measures, cardiovascular disease and cardiovascular mortality than those whose CRF declines. However, these previous studies are limited for several reasons, including use of a largely male population, measurement of fitness over a limited duration (5-7 years) or measurement of fitness at varying intervals prospectively. In this new research, the authors used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to objectively and rigorously analyse the link between CRF and development of either prediabetes or diabetes over a 20-year period.

The authors proposed that higher fitness levels, even after adjusting for changes in BMI, would be associated with reduced risk for developing incident prediabetes/diabetes. The CARDIA study consisted of 4,373 black and white women and men who were recruited and examined in 1985-1986 from four US communities (Birmingham, AL; Chicago, IL; Minneapolis, MN and Oakland, CA) and balanced on age, race, sex and educational attainment. CRF was assessed prospectively by treadmill exercise testing at baseline (Year 0 [Y0]: participants aged 18-30 years), early adulthood (Y7: the same participants now aged 25-37 years) and again at middle age (Y20: the same participants, now aged 38-50 years). Development of prediabetes/diabetes was ascertained during scheduled visits (at Y0, Y7, Y10, Y15, Y20, and Y25) for the CARDIA study.

The main finding is that higher CRF is associated with lower risk for developing prediabetes and diabetes, even when adjusting for prospective changes in body mass index. Although higher CRF may be influenced by genetic factors, physical activity is well known to increase CRF. This study found that when using treadmill exercise testing to measure CRF, an 8-11% higher fitness level reduced the risk for developing prediabetes or diabetes by 0.1%. For context, achieving this higher level of fitness was examined by another study* and required either vigorous physical activity for 30 minutes daily, 5 days per week or moderate physical activity for 40 minutes daily, 5 days per week. While the CARDIA study found that the overall reduction in risk for prediabetes/diabetes was modest at the individual level, these changes remain significant at the population level where small changes in a large number of individuals may lead to large absolute reduction in prediabetes/diabetes.

The authors conclude: "This study is clinically relevant as it provides evidence to support commonly accepted dogma that fitness is beneficial in reducing the risk for prediabetes/diabetes. As this benefit remained significant even when adjusting for BMI, exercise programmes remain critically important for reducing the development of prediabetes and diabetes."

Attending religious services associated with lower risk of death in women

Frequently attending religious services was associated with a lower risk of death for women from all causes, cardiovascular disease and cancer, according to a new study published online by JAMA Internal Medicine.

Religious practice is common in the United States but the effects of religious practice on health are not clear.

Tyler J. VanderWeele, Ph.D., of the Harvard T.H. Chan School of Public, Boston, and coauthors used data from the Nurses' Health Study in an analysis examining attendance at religious services and subsequent death in women. Attendance at religious services was assessed in questionnaires from 1992 to 2012; data analysis was conducted from the 1996 questionnaire to 2012 for a 16-year follow-up.

Among 74,534 women at the 1996 study baseline with reported religious service attendance, 14,158 attended more than once a week, 30,401 attended once per week, 12,103 attended less than once per week and 17,872 never attended. Most of the study participants were Catholic or Protestant. Women who frequently attended religious services tended to have fewer depressive symptoms, were less likely to be current smothers and more likely to be married.

Among the 74,534 women, there were 13,537 deaths, including 2,721 from cardiovascular disease and 4,479 from cancer.

Women who attended religious services more than once per week had a 33 percent lower risk of death during the 16 years of follow-up compared with women who never attended religious services. Women who attended services weekly had a 26 percent lower risk and those who attended services less than weekly had a 13 percent lower risk, according to the results.

The study indicates women who attended religious services more than once a week had a 27 percent lower risk of death from cardiovascular disease and a 21 percent lower risk of death from cancer compared with women who never attended.

The authors note depressive symptoms, smoking, social support and optimism were potentially important mediators of the association between attending religious services and death.

However, the authors note limits in the generalizability of their results because the study mainly consisted of white Christians and the participants were nurses with similar socioeconomic status and who were health conscious. This observational study also cannot imply causality and the authors note that a randomized clinical trial of attendance at religious services is neither ethical nor feasible.

"Religion and spirituality may be an underappreciated resource that physicians could explore with their patients, as appropriate," the authors conclude.

Commentary: Empirical Studies about Attendance at Religious Services, Health

"In this issue of JAMA Internal Medicine, Li et al report a clear and moderately strong association between attendance at religious services and decreased mortality during a 16-year follow-up of a subgroup from the Nurses' Health Study. ... First, readers and investigators must, as do these authors, focus on the data, no more and no less, and not attempt to generalize beyond the evidence. ... So what can we learn from this study? In this well-designed secondary data analysis, attendance at religious services is clearly associated with lower risk of mortality. This finding should not be ignored but rather explored in more depth," writes Dan German Blazer, II, M.D., M.P.H., Ph.D., of Duke University Medical Center, Durham, N.C., in a related commentary.