Statins not associated with memory or cognition decline in elderly

Given consumer concern that statins may be associated with memory or cognitive decline, a new study published today in the Journal of the American College of Cardiology may offer reassurance, as no difference was found in the rate of memory or cognitive decline of elderly statin-users compared to never-users.
"Not only are statins one of the most prescribed medications in the world, there is strong evidence that they reduce mortality in our patients with heart disease, stroke, diabetes, renal disease and other lipid disorders. Most importantly, statins aren't associated with a risk for major adverse health advents," said Katherine Samaras, MBBS, PhD, an endocrinologist at St. Vincent's Hospital in Australia and the study's lead author. "These findings will hopefully go a long way toward reducing consumers' concerns about memory and cognition from statins, so they don't stop taking these lifesaving medications."
The researchers examined changes in the memory and global cognition regarding statin-use over a six-year observation period and two years of brain volume studies using the Sydney Memory and Ageing Study, a longitudinal observation study of cognition of community-dwelling, non-demented elderly participants conducted at the Centre for Healthy Brain Ageing (CHeBA), University of New South Wales, Sydney, Australia. Data were collected every two years on four occasions over the six-year period by psychologists and nurses. Clinicians diagnosed the presence of heart disease, cerebrovascular disease, hypertension and Type 2 diabetes.
Participants' medications and duration of use were categorized as statin ever-use versus never-use; continuous statin-use during observation versus never-use; specific statins (simvastatin, pravastatin and atorvastatin) versus never-use; and statin initiation during observation period versus never-use.
The 1,037 participants were aged 70 to 90 years and were 98% Caucasian and Australian- (67%) or European- (18%) born. There were 395 statin never-users and 642 statin ever-users, which included ever-users at baseline and those who commenced taking statins during the study period. On average, participants had been on statins for nine years.
To measure their primary endpoints--memory and global cognition--a comprehensive assessment of global cognition and memory was developed. Five memory tests were employed by the researchers to assess new learning and short and long-term recall using verbal and visual memory tasks. Global cognition evaluated memory plus processing speed, language, visuospatial ability and executive function.
All participants were offered brain magnetic resonance imaging (MRI) at baseline, with 529 patients accepting and 408 undergoing a repeat MRI two years later. Statin ever-users and never-users were found to have similar total brain volume, hippocampal and parahippocampal brain volumes at baseline with no significant differences two years later.
Statin ever-users and never-users were similar at baseline for both memory and global cognition, the researchers found no significant difference in rate of decline in either memory or global cognition. Participants who took statins continuously over the study period had significantly higher baseline performance in memory and global cognition compared to never-users; the rate of decline in memory and global cognition for this subgroup was similar over the six-year observation period. When researchers compared the 99 participants who started statins during the study period, they found statin initiation was associated with a lessening in the rate of decline of memory. Overall, no associations between statin use and cognition were found between baseline and the six years of observation.
The researchers did find a protective interaction between statin ever-use, heart disease and the six-year change in the total learning memory test score. Among patients with heart disease, statin ever-users displayed a slower rate of decline on this test compared to never-users. However, in patients without heart disease, there was a comparable rate of decline between statin ever-users and never-users. The study also found a protective interaction between statin ever-use and the rate of decline in long-delayed recall performance for patients carrying the APOE-4 genotype. Carriers of this genotype are at high risk of Alzheimer's disease. In secondary analyses, male statin users did display a significantly faster logical memory decline compared to male never-users, but there was no significant difference between female statin users and never-users.
"We must acknowledge some limitations of the study, in particular the observational design and potential for selection and survivor bias," said Perminder Sachdev, MBBS, PhD, senior author who, along with Henry Brodaty, MBBS, MD, leads the Sydney Memory and Ageing Study. "Additionally, as participants with more advanced cognitive impairment were excluded from the study, no conclusions can be made for statin benefits in that group."
In an accompanying editorial, Costantino Iadecola, MD, and Neal S. Parikh, MD, MS, from Weill Cornell Medicine in New York City said, "These data support the view that worries about cognitive impairment should not limit statin use and raise the possibility that statins may favorably alter cognitive trajectories in a group of elders at high risk of Alzheimer's disease."

High-protein diets may harm your kidneys

A high-protein diet is believed to be healthy. It is suggested that it keeps you fit, helps you to lose fat and to retain lean muscle mass. Avoiding carbohydrates and substituting them with proteins has become a leading dogma for all those who care for their looks and health.

Kamyar Kalantar-Zadeh, Holly M Kramer and Denis Fouque [1] now consider it necessary to question this belief and to put a tough warning label on our modern eating habits. "We may save calories, but we may also risk the health of our kidneys." The promise of saving calories and losing weight is why a high-protein diet is very often recommended to people who suffer from diabetes or who are obese. But the crux of the matter is that these groups of people are especially vulnerable to the kidney-harming effects of a high protein intake.

"A high-protein diet induces glomerular hyperfiltration, which, according to our current state of knowledge, may boost a pre-existing low-grade chronic kidney disease, which, by the way, is often prevalent in people with diabetes. It might even increase the risk of de novo kidney diseases", explains Prof Fouque, past-chair of the European Renal Nutrition Working Group. "To put it in a nutshell: To recommend a high-protein diet to an overweight diabetes patient may indeed result in loss of weight, but also in a severe loss of kidney function. We want one, but we also get the other."

In view of the rising number of people affected by type-2 diabetes, and the fact that at least 30% of patients with diabetes suffer from an underlying chronic kidney disease, the experts believe it is high time that the diabetes population and the general public are warned. "By advising people - especially those with a high risk for chronic kidney disease, namely patients with diabetes, obese people, people with a solitary kidney and probably even elderly people - to eat a protein-rich diet, we are ringing the death bell for their kidney health and bringing them a big step closer to needing renal replacement therapy", says Fouque.

This is the essence of the editorial by the three authors mentioned above, which has been published along with two new studies on that topic in the current issue of NDT. The analysis of a Dutch cohort [2] showed a strictly linear association between daily protein intake and decline in kidney function. The higher the intake, the faster the decline. The result of an epidemiological study conducted in South Korea [3] points to the same direction: Persons with the highest protein intake had a 1.3 higher risk of faster GFR loss. The finding itself is not new. Many previous studies have shown that a high-protein diet may harm kidney function, and this is why patients with a known early-stage chronic kidney disease are recommended a low-protein diet by their nephrologists. As long as it is unclear whether it makes any difference if the proteins are animal- or plant-based, the recommendation is to abstain in general from a high protein intake.
However, as Fouque and his colleagues point out, the problem are the people who have a mild chronic kidney disease which they are totally unaware of and who follow the trend of eating a protein-rich diet because they believe it is healthy. "These people do not know that they are taking the fast lane to irreversible kidney failure". Prof Fouque and his ERA-EDTA colleagues want to start an information campaign and raise awareness for this problem among the general population. "It is essential that people know there is another side to high-protein diets, and that incipient kidney disease should always be excluded before one changes one eating habits and adopts a high-protein diet."

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[1] Kamyar Kalantar-Zadeh, Holly M Kramer, Denis Fouque. High-protein diet is bad for kidney health: unleashing the taboo. Nephrology Dialysis Transplantation, gfz216, https://doi.org/10.1093/ndt/gfz216
[2] Esmeijer K, Geleijnse JM, de Fijter JW et al. Dietary protein intake and kidney function decline after myocardial infarction: the Alpha Omega Cohort. Nephrology Dialysis Transplantation, gfz015, https://doi.org/10.1093/ndt/gfz015
[3] Jhee J-H, Kee Y-K, Park S et al. High-protein diet with renal hyperfiltration is associated with rapid decline rate of renal function: community based prospective cohort study. Nephrol Dial Transplant 2019. https://doi.org/10.1093/ndt/gfz115
About ERA-EDTA
With more than 7,000 active members, the ERA-EDTA is one of the biggest nephrology associations worldwide leading European nephrology and one of the most important European Medical Associations. It organizes annual congresses and a Scientific Education Interactive Day (SEID), it produces guidelines, collects data and performs epidemiological studies through its Registry. It supports fellowships and research projects. Its publications are NDT and CKJ (this last journal is Open Access). The ERA-EDTA also has an online Educational platform: the European Nephrology Portal (ENP) which includes NDT-Educational@ENP. The 2020 Congress will be held June 6-9 in Milan (Italy). Visit the booth to receive more information! Web site: http://www.era-edta.org

Nearly half of 50- to 64-year-olds think they're likely to develop dementia, but few have talked to a doctor reducing their risk and many use unproven tactics

Nearly half of Americans in their 50s and early 60s think they're likely to develop dementia as they grow older, but only 5% of them have actually talked with a doctor about what they could do to reduce their risk, a new study finds.
Meanwhile, a third or more say they're trying to stave off dementia by taking supplements or doing crossword puzzles - despite the lack of proof that such tactics work.
The new findings suggest a need for better counseling for middle-aged Americans about the steps they can take to keep their brains healthy as they age.
Meanwhile, pharmaceutical companies continue to work on potential dementia-preventing medications. But an over-estimation of future dementia risk by individuals may lead to costly over-use of such products, the researchers warn.
The new results appear in a research letter in the new edition of JAMA Neurology, and a presentation at the Gerontological Society of America's annual meeting.
Both are by members of a team from the University of Michigan's Institute for Healthcare Policy and Innovation who analyzed data from a nationally representative poll of 1,019 adults between the ages of 50 and 64.
Donovan Maust, M.D., M.S., a geriatric psychiatrist specializing in dementia-related care and lead author of the JAMA Neurology letter, notes that even among the oldest Americans, the risk of dementia is lower than one in three people over age 85.
Risk starts rising around age 65, and is higher among people of Latino or African-American heritage.
When people are in their 50s and early 60s, he says, they still have time to bring down their future dementia risk.
"There is growing evidence that adults in mid-life can take steps to lower their risk of dementia, including increasing physical activity and controlling health conditions like hypertension and diabetes," says Maust. "Unfortunately, our findings suggest that people may not be aware of this and are not asking their doctor."
Meanwhile, the new study shows, 32% of those polled said they were taking fish oil or omega-3 fatty acid supplements, and 39% said they took other supplements for brain health. More than half said they were doing crossword puzzles or other brain games in hopes of keeping their minds "sharp."
Other findings
The new data come from the National Poll on Healthy Aging, carried out by IHPI with support from AARP and Michigan Medicine, U-M's academic medical center. The new paper, and GSA presentation by poll co-director Erica Solway, Ph.D., M.S.W., delve deeper into the poll data than the report issued earlier this year.
The level of worry about dementia among some groups of middle-aged adults may not be in line with their risk compared to others, the study suggests. For example, studies suggest that people of Latino heritage are about 50% more likely to develop dementia than non-Latino whites, and African-Americans are about twice as likely as non-Latino whites.
However, in the poll, those of African-American or Latino backgrounds did not consider themselves more likely to develop dementia than white respondents.In fact, African-American respondents felt they were significantly less likely to develop dementia than other groups.
Similarly, middle-aged people with worse physical health because of conditions such as diabetes, high blood pressure and heart disease are more likely to develop dementia than those in good health. However, poll respondents who reported their physical health as just fair or poor did not judge their risk of dementia to be higher than their healthier peers.
Turning worry into prevention
Reducing the risk of developing dementia can be done in mid-life through things like increasing physical activity, smoking cessation, and managing chronic medical conditions such as diabetes or hypertension, says Maust.
Physicians and public health authorities should communicate to middle-aged adults that taking these steps are the most evidence-based strategies to help preserve brain function into old age, Maust says, as well as reducing the risk of everything from heart attacks and strokes to lung disease, cancer and loss of vision and mobility.
Even if drug developers succeed where past attempts have failed, and come up with medications that act specifically to prevent dementia, those drugs are likely to be costly. And the failure of several would-be preventive drugs mean it could be years before one hits the market.
But people in their 50s and 60s can take specific actions to improve their health now at much lower cost to themselves and society, plus saving the dollars they've been spending on supplements and brain games.

Unhealthy habits can start young: Infants, toddlers, and added sugars

A new study in the Journal of the Academy of Nutrition and Dietetics breaks new ground by evaluating a nationally representative sample of infant and toddler diets and consumption of added sugars

IMAGE: Top eight sources of added sugars in the diets of US infants and toddlers aged 6 to 23 months, National Health and Nutrition Examination Survey, 2011-2016. view more 

Credit: CDC/NCHS, National Health and Nutrition Examination Survey, 2011-2016

Philadelphia, November 14, 2019 - A new study in the Journal of the Academy of Nutrition and Dietetics, published by Elsevier, found that nearly two-thirds of infants (61 percent) and almost all toddlers (98 percent) consumed added sugars in their average daily diets, primarily in the form of flavored yogurts (infants) and fruit drinks (toddlers). Infants were 6-11 months, and toddlers were 12-23 months.
The analysis documented some good news in the decline over the study period (2005-6 and 2015-16) in the percentage of infants and toddlers whose daily diets include added sugars, as well as the amounts they consumed. Yet the widespread intake points to a serious and persistent problem: the early development of eating patterns associated with negative health conditions.
"Our study, which is the first to look at trends in added sugars consumption by infants and toddlers, documents that most infants and toddlers consume added sugars. This has important public health implications since previous research has shown that eating patterns established early in life shape later eating patterns," explained lead investigator Kirsten A. Herrick, PhD, MSc, Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD, USA. She cited an earlier study that found that 6-year-olds who had consumed any sugar-sweetened beverage (SSB) before the age of one were more than twice as likely to consume an SSB at least once a day compared to 6-year-olds who had not consumed any before the age of one.
Dr. Herrick noted, "Previous research into the diets of children over two years old associated sugar consumption with the development of cavities, asthma, obesity, elevated blood pressure and altered lipid profiles."
Health organizations in the United States promulgate guidelines that recommend limiting sugar intake to 9 tsp or less for adult men, and 6 tsp or less for adult women and children between 2 and 19. With no comparable research available for infants and toddlers prior to this study, only one organization, the American Heart Association, provided any guidance for children under age 2. "Our study's findings about infant and toddler diets should raise awareness among health organizations and practitioners and inform future guidelines and recommendations," she added.
The investigators analyzed data for 1,211 infants and toddlers (6-23 months) from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, a nationally representative study conducted by the US Centers for Disease Control and Prevention. They used the Food Patterns Equivalents Database and the United States Department of Agriculture's What We Eat In America's list to categorize foods. Sugars contained in breast milk and formula were not included in the consumption estimates.
The results showed that infants consumed about 1 teaspoon (tsp) of added sugars daily (equivalent to about 2 percent of their daily caloric intake), while toddlers consumed about 6 tsp of sugars (about 8 percent of their daily caloric intake). No differences were detected in added sugars consumption by sex, family income level, and head-of-household, but there were some distinctions by race/Hispanic origin: non-Hispanic Asian toddlers consumed the fewest added sugars (3.7 tsp) and non-Hispanic black toddlers consumed the most added sugars (8.2 tsp). The top food sources of added sugars for infants included yogurt, baby snacks and sweets, and sweet bakery products. For toddlers, the top sources included fruit drinks, sweet baked products, and sugar and candy.
According to Dr. Herrick, parents should be mindful of added sugars levels in the foods chosen when weaning their infants. "The transition from a milk-based diet (breast milk and formula) to table foods has an impact on nutrition, taste preference, and eating patterns. More work is needed to understand this critical period." She recommends discussing which solid foods to introduce during weaning with a child's healthcare provider and pointed to the Nutrition Facts label as another resource to support informed decisions. While the federal requirement to include added sugars content of a food or beverages on the Nutrition Facts label is not mandatory until January 2020, many labels already include this information. For more information about infant and toddler nutrition, visit http://www.cdc.gov/nutrition.
In September 2019, the Academy of Nutrition and Dietetics joined the American Heart Association, the American Academy of Pediatric Dentistry, and the American Academy of Pediatrics to recommend breast milk, infant formula, water, and plain milk as part of a new set of comprehensive beverage recommendations for children, outlined by age (birth through age 5). They caution against beverages that are sources of added sugars in young children's diets, including flavored milks (e.g., chocolate, strawberry) and sugar- and low-calorie sweetened beverages, in addition to a wide variety of beverages that are on the market and targeted to children that provide no unique nutritional value.

Improved fitness can mean living longer without dementia

Staying fit or improving fitness over time should be a goal for anyone who wants to reduce the likelihood of getting dementia.

"It is important to say that it is never too late to begin exercising. The average participant in our study was around 60 years old at baseline, and improvement in cardiorespiratory fitness was strongly linked to lower dementia risk. Those who had poor fitness in the 1980s but improved it within the next decade could expect to live two years longer without dementia," says Atefe Tari of the Cardiac Exercise Research Group (CERG) at the Norwegian University of Science and Technology (NTNU).
Tari is lead author of a new study that was recently published in Lancet Public Health, a highly ranked journal in the prestigious Lancet family.
"Persistently low fitness is an independent risk factor for dementia and death due to dementia," the authors concluded.
The higher, the better
Dementia involves a progressive decline in cognitive functions, severe enough to interfere with the ability to function independently. Alzheimer's disease is the most common form of dementia.
By 2050, it is estimated that 150 million people in the world will have dementia - a tripling of the incidence of the disease today. There is no cure. Men live on average five years after being diagnosed with dementia, while women live for seven years on average after the diagnosis.
"As there is currently no effective drug for dementia, it is important to focus on prevention. Exercise that improves fitness appears to be one of the best medicines to prevent dementia," says Tari.
Tari's study is far from the first to show a link between good fitness and lower risk of getting dementia. What is unique, however, is that Tari and her research colleagues have measured the fitness level of participants twice ten years apart.
Thus, they have been able to evaluate how changes in fitness over time are related to dementia risk. And the results were clear.
Exercise that improves fitness appears to be one of the best medicines to prevent dementia.
"If you increase your cardiorespiratory fitness from poor to good you almost halve the risk of getting dementia. You also reduce the risk of dying from or with dementia. In our study, each increase of 1MET was associated with a 16% lower risk of getting dementia and a 10% lower risk of dementia-related death. This is an improvement that is very achievable for most people", says Tari.
A MET is a measurement unit used by researchers to quantify the rate at which a person expends energy relative to their body weight.
Followed for 30 years Between 1984 and 1986, almost 75,000 Norwegians participated in the first wave of the HUNT Survey (HUNT1). Eleven years later, HUNT2 was organized, and 33,000 of the same people participated. More than 30,000 of them answered enough questions to be included in Tari's analyses.
The researchers calculated cardiorespiratory fitness with a formula previously developed and validated by the Cardiac Exercise Research Group, called the Fitness Calculator.
Previous studies have shown that those who score poorly on this calculator have an increased risk of heart attack, atrial fibrillation, depression and non-alcoholic fatty liver disease, and also that they generally die younger than people who achieve a higher fitness level.
The new study links results from the Fitness Calculator to the risk of dementia and dementia-related deaths up to 30 years later. To investigate these associations, Tari has used data from two different databases, the Health and Memory Study in Nord-Trøndelag and the Norwegian Cause of Death Registry.
Almost half the risk Between 1995 and 2011, 920 people with dementia were included in the Health and Memory Study in Nord-Trøndelag. A total of 320 of them had also participated in both HUNT1 and HUNT2 and provided enough information about their own health to be included in the analyses.
It turned out that poor cardiorespiratory fitness in both the 1980s and 1990s was significantly more common in this group than among otherwise comparable HUNT participants who had not been diagnosed with dementia.
In fact, the risk of developing dementia was 40% lower for those who were among the 80% with the best fitness in both the 1980s and 1990s. Furthermore, it was 48% lower if one had changed from poor to higher fitness levels between the two surveys.
All participants were followed until death or end of follow-up in the summer of 2016. Via the Norwegian Cause of Death Registry, the NTNU researchers found 814 women and men who had died from or with dementia during the period. This means that dementia was stated as the underlying, immediate or additional cause of death.
The risk was lowest for those who had good fitness at both HUNT surveys. However, also those who had changed from poor to better fitness over the years had a 28% reduced risk.
Cause or coincidence?
In observational studies, there will always be questions about cause-effect relationships. For example, one might ask what causes what: Is it bad fitness that weakens the brain, or do people with cognitive impairment find it more difficult to be physically active and increase their fitness?
"Our study made it easy to see which came first. We estimated the fitness of the participants for the first time in the 1980s, and looked for dementia cases and deaths from 1995 onwards. We have also done separate analyses where we excluded those who got dementia or died during the first few years of the follow-up period, and the results were the same," says Tari.
It's also reasonable to ask if the association is random; it might not be the poor fitness that increases the risk of dementia, but people with poor fitness might also have several of the more well-known risk factors for dementia - such as high blood pressure, low level of education and a family history of brain diseases. That is an unlikely explanation, says Tari.
"The HUNT studies give us very broad information about the health of the participants, including body composition, smoking habits, educational level, blood pressure, diabetes, cholesterol levels and family history of stroke. By adjusting the analyses for these factors, we have ruled out that they fully explain the relationship between fitness and dementia risk in our study," she says.
Physical activity vs. fitness In other words, the study provides very good evidence that maintaining good fitness is also good for the brain. However, Tari points out that this does not necessarily mean that everyone who is physically active on a regular basis is guaranteed that a good effect on brain health.
"High-intensity exercise improves fitness faster than moderate exercise, and we recommend that everyone exercise with a high heart rate at least two days each week. Regular exercise that makes you sweaty and out of breath will ensure your fitness will be good for your age. Our study suggests that good fitness for your age can delay dementia by two years and that you can also live two to three years longer after being diagnosed with dementia," she said.

Take a yoga class and depression, anxiety improve

Scientific studies already support yoga practice as a means to reduce symptoms of depression and anxiety. Now a new study out of Boston University School of Medicine (BUSM) provides evidence that yoga and breathing exercises can improve symptoms of depression and anxiety in both the short term--with each session as well as cumulatively in the longer term, over three months.
Published online in the Journal of Psychiatric Practice, these findings suggest yoga can be a helpful complementary treatment for clinical depression or major depressive disorder.
A group of 30 clinically depressed patients were randomly divided into two groups. Both groups engaged in lyengar yoga and coherent breathing with the only difference being the number of instructional and home sessions in which each group participated. Over three months, the high-dose group (HDG) spent 123 hours in sessions while the low-dose group (LDG) spent 87 hours.
Results showed that within a month, both groups' sleep quality significantly improved. Tranquility, positivity, physical exhaustion and symptoms of anxiety and depression significantly improved in both groups, as measured by several validated clinical scales
"Think of it this way, we give medications in different doses in order to enact their effects on the body to varying degrees. Here, we explored the same concept, but used yoga. We call that a dosing study. Past yoga and depression studies have not really delved deeply into this," explained corresponding author Chris Streeter, MD, associate professor of psychiatry at BUSM.
"Providing evidence-based data is helpful in getting more individuals to try yoga as a strategy for improving their health and well-being. These data are crucial for accompanying investigations of underlying neurobiology that will help elucidate 'how' yoga works," said study collaborator and co-author Marisa M. Silveri, PhD, neuroscientist at McLean Hospital and associate professor of psychiatry at Harvard Medical School.
Depression, a condition that affects one of every seven adults in the U.S. at some point in their lives, is treated with a variety of modalities, including counseling (especially through cognitive-behavioral therapy) and medication. Research has shown combining therapy and medication has greater success than either treatment alone. Although studies with more participants would be helpful in further investigating its benefits, this small study indicates adding yoga to the prescription may be helpful.

Fracture risk for patients taking multiple medications

There is a strong association between the number of fracture-associated drugs (FADs) older patients receive and their risk of sustaining a broken bone, according to a new Dartmouth study published in JAMA Network Open.
In recent decades, the use of prescription medications has increased dramatically in the U.S. due to factors such as improvements in the ability to detect disease, expanding treatment options, and an aging population. For many older Americans (over age 65), these medications provide an effective means of managing disease and improving both quality of life and longevity.
But many commonly prescribed drugs, such as opioid pain killers, antidepressants, antacids, and sleep aids, are known to carry an increased risk of breaking a bone (by increasing falls, weakening bones, or both). This is especially true for patients whose fracture risk is already high due to conditions like osteoporosis.
"With older adults consuming, on average, five medications simultaneously, we suspected that a good number of seniors are likely to use more than one of these fracture-associated drugs at a time," explains Rebecca Emeny, PhD, MPH, a research scientist at The Dartmouth Institute for Health Policy and Clinical Practice and lead author on the study. "We wanted to determine how that increased exposure would impact their risk for hip fractures, which are among the most painful, debilitating, deadly, and costly fractures one can experience."
In the study, the researchers looked at the prescription records of 2.5 million Medicare beneficiaries (from 2004-2014)--determining how many and which of 21 FADs were being taken--and found that these drugs were commonly used and commonly combined among older U.S. residents. They identified hip fracture diagnosis codes from inpatient claims, used statistical analysis to measure the risk of hip fracture associated with each medication, and then compared their findings to the hip fracture risk experienced by people who took none of the FADs.
The investigators were not surprised to find that the more fracture-associated medicines people took, the higher their fracture risk, but the size of the additional risk was more than they expected. On average, taking any one of these drugs doubled a person's risk, taking any two almost tripled it, and taking three or more increased fracture risk four-fold.
The most commonly taken FADs (alone or in combination with others) were opioids, used by 55 percent of the cohort, followed by diuretics at 40 percent, and proton pump inhibitors (PPIs), used to treat acid reflux, at 35 percent.
"While the average effect of FADs was interesting, we expected some drug combinations would be riskier than others," she says. "To explore this, we measured the risk associated with each of the 21 drugs and with each of the 210 pairs one could create with these 21 drugs."
The most hazardous combinations were found to be opioids and sedatives, opioids and diuretics, and opioids and PPIs. Notably, many risky pairs of FADs included potentially avoidable drugs.
"This is an important consideration for patients, if any of their medications are optional and thus can be eliminated with no negative consequences," says corresponding author Nancy Morden, MD, MPH. "In any case, the results of our cohort study suggest caution when combining FADs, especially when use is discretionary, alternatives exist, or baseline fracture risk is high."