Excess sitting linked to coronary artery calcification



Excess sitting linked to coronary artery calcification, an early indicator of heart problems


Date: March 5, 2015




American College of Cardiology


Sitting for many hours per day is associated with increased coronary artery calcification, a marker of subclinical heart disease that can increase the risk of a heart attack, according to research scheduled for presentation at the American College of Cardiology's 64th Annual Scientific Session in San Diego.


Coronary artery disease is the most common type of heart disease and the leading cause of death in the United States.


The study found no association between coronary artery calcification and the amount of exercise a person gets, suggesting that too much sitting might have a greater impact than exercise on this particular measure of heart health.


The results suggest that exercise may not entirely counteract the negative effects of a mostly sedentary lifestyle on coronary artery calcium.


"It's clear that exercise is important to reduce your cardiovascular risk and improve your fitness level," said Jacquelyn Kulinski, M.D., assistant professor of cardiovascular medicine at the Medical College of Wisconsin and the study's lead author.


"But this study suggests that reducing how much you sit every day may represent a more novel, companion strategy (in addition to exercise) to help reduce your cardiovascular risk."


The research comes on the heels of recent studies linking excess sitting with an increased risk for cardiovascular disease, diabetes, cancer and early death.


The phenomenon has been dubbed "sitting disease," though it is a lifestyle risk factor and not a true medical condition.


This study offers a unique perspective on the effects of sedentary behavior because it links sitting with an early marker for heart disease risk, laying the foundation for future studies that could investigate whether changing your habits could potentially reverse the damage before you develop full-blown heart disease.



Coronary artery calcification, measured through a non-invasive CT heart scan, indicates the amount of calcium contained in plaques within the heart's arteries.


Coronary artery disease occurs when such plaques accumulate over time, causing the arteries to narrow.


Analyzing heart scans and physical activity records of more than 2,000 adults living in Dallas, the researchers found each hour of sedentary time per day on average was associated with a 14 percent increase in coronary artery calcification burden.


The association was independent of exercise activity and other traditional heart disease risk factors.


"I think the study offers a promising message. Reducing the amount of time you sit by even an hour or two a day could have a significant and positive impact on your future cardiovascular health," Kulinski said.


A particular strength of the study is that the researchers used a motion-tracking device called an accelerometer to measure how long participants were sedentary and how much they exercised, whereas most previous studies have relied on surveys.


"With surveys, there's more subjectivity," Kulinski said. "With this device, we're able to log activity levels minute-by-minute."


The results revealed participants sat for a little more than five hours per day on average, with a range of two to 12 hours. More sedentary participants were more likely to be older, have a higher body mass index, and have diabetes or hypertension.


The analysis accounted for these factors, as well as for income, marital status, smoking, cholesterol, and other demographic and health-related factors. People with known cardiovascular disease, such as a previous stroke or heart attack, were excluded from the analysis.


"The lesson here is that it's really important to try to move as much as possible in your daily life; for example, take a walk during lunch, pace while talking on the phone, take the stairs instead of the elevator and use a pedometer to track your daily steps," Kulinski said. "And if you do have a very sedentary job, don't go home at night and sit in front of the TV for hours on end."


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American College of Cardiology. "Excess sitting linked to coronary artery calcification, an early indicator of heart problems." ScienceDaily. ScienceDaily, 5 March 2015.



Is Calcium Good or Bad?

George D. Lundberg, MD
February 03, 2015
Hello and welcome. I am Dr George Lundberg and this is At Large at Medscape.
How is your calcium? Is it good or bad? Does it help you or hurt you? Where is it? Evaluating calcium in humans is a lot like evaluating a piece of real estate: It is all about location, location, location.
First, the good places: More than 99% is in teeth, bones, or blood and intra- and extracellular fluid.
Then, the bad places: soft tissues; kidneys and urinary tract; artery and vein walls; tumors; female breasts; or as part of resolving necrosis or cellular degeneration.
How does it get there? Calcium in, calcium out. Calcium in: maybe a supplement of 1000 mg/day orally for an adult. Calcium out: via urine and feces, with the retained calcium being managed by spectacular metabolic homeostasis. It is a very delicate balance.
One of the ways that calcium appears in seemingly unwanted locations is called "dystrophic calcification," and its presence seems relatively inert.
Can you move calcium around in the body? Maybe not moving individual calcium moieties from place to place, but can you regulate how much of what kind of calcium is in any one place at any one time?
Like the Blind Man and the Elephant: Point of View Matters
The nutritionists would say: This is all about diet.
The endocrinologists would say...a lot; they really know this field.
The imagers would say: I love calcium; it gives me so many fun things to look at, measure, and analyze to try to predict importance.
The urologists would say: I can take care of your stones. We will flush them out or pluck them out or shake them into small pieces with the lithotripter.
And by the way, here is your $30,000 bill.
The mammographers and breast surgeons would say: If I did not have calcium flecks to find in the mammogram, I might have a really hard time justifying biopsies.
The procedural interventionists would say: Send me your calcified arteries; I have a stent for you.
Big pharma would say: We have lots of drugs.
The outlier chelationists would say: We can give you some IV infusions to get rid of all that bad stuff.
As a pathologist, I have cut—or, more accurately, sawed—a whole lot of bones, healthy and diseased. It is really good to have a lot of calcium as hydroxyapatite there, in the bone. I have cut up a lot of kidneys destroyed by stones obstructing the urinary tract. Calcium can be really bad to have there.
I have longitudinally opened or perpendicularly transected many hundreds of large and small arteries; many normal, many diseased by narrowing; many occluded by atherosclerotic plaque, intraplaque hemorrhage, cholesterol, thrombus (acute, evolving, organized, or recanalized), and calcified; sometimes very thick, hard, brittle, even rigid; and especially in arteries of hearts, brains, necks, chests, bellies, legs. Bad.
But which came first: the chicken or the egg? Was the vascular wall calcium an instigating progenitor, a fellow traveler as simple dystrophy, a part of the inflammatory pathogenesis, or a culminating bony add-on for advanced atherosclerosis? Those are really good questions.
Here's the new stuff. A large volume of alternative literature has been hyping vitamin K2 as active in preventing or treating arterial calcification for years. But serious science now seems to be backing that up.
The relationship of vitamin D, vitamin K2, and calcium may hold a real key to a better understanding of harmful arterial calcification. Check it out; keep an open mind; stay tuned.
That is my opinion. I am Dr George Lundberg, at large for Medscape.
Medscape Internal Medicine © 2015  WebMD, LLC

Cite this article: Is Calcium Good or Bad? Medscape. Feb 03, 2015.

اختبار بسيط يكشف إصابة الأحياء والموتى بـ«إيبولا» فى غضون 10 دقائق





برلين ـ من محمد السيد طورت شركة أدوية ألمانية، أشرطة اختبار سريعة يمكنها تشخيص إصابة البشر (الأحياء والموتى) بعدوى فيروس إيبولا القاتل، في غضون 10 دقائق، وسيتم طرحها فى الأسواق بداية من آذار/مارس المقبل.


وقالت شركة «ستادا» (STADA) الألمانية للمستحضرات الطبية، فى بيان نشرته على موقعها على الإنترنت أمس، إن الاختبار الجديد ابتكرته وانتجته شركة «سينوفا» (Senova) الألمانية لمعدات التشخيص، بينما ستتولى «ستادا» تسويقه.


ويتطلب الفحص المعتاد للكشف عن إيبولا وقتًا أطول، كما يتطلب مختبرات حديثة للكشف وهى غير متوفرة فى أغلب المناطق الموبوءة بالمرض فى غرب أفريقيا، لكن الفحص الجديد، يعمل من خلال وضع عينات من سوائل الجسم على شريط الاختبار، على غرار شريط اختبار الحمل التقليدي، كما أنه يناسب ظروف التخزين فى درجة حرارة الغرفة، وهو ما يجعله مناسبًا لدول العالم الثالث.


وأضاف البيان أنه تمت تجربة مدى فاعلية الاختبار الجديد لدى مئات المشاركين في هذه التجارب بغينيا.


وأوضحت الشركة ان الاستخدام الرئيسي للاختبار سينصب على تشخيص حالات الوفاة، لأن سوائل الجسم لدى المتوفين لا تحتاج الى معالجة سابقة قبل الاختبار، كما أن مخالطة المشيعين من أقارب المتوفين لجثثهم من الأسباب الشائعة لانتقال عدوى إيبولا، وخاصة فى المناطق الموبوءة.


وقال «هانز هيرمان زوفينج» مالك شركة «ينوفا» إن «عدد الفيروسات الموجودة في أجساد المتوفين بإيبولا عال للغاية، لدرجة أن مجرد مسحة من الحلق تكفي لإجراء هذا الاختبار السريع».


وأشارت شركة «ستادا» إلى أن الاستعانة بالاختبار الجديد للكشف عن إصابة الأشخاص الأحياء بفيروس إيبولا، ستتطلب بالضرورة معالجة مسبقة لعينات من الدم، من خلال أجهزة طرد مركزي تعمل بالبطاريات، وهي معدات متوافرة لدى معظم مراكز إغاثة الطوارئ في المناطق المتضررة.


وعن سعر الاختبار الجديد، قالت شركة «ستادا» إنها ستبدأ توزيعه فى آذار/مارس المقبل، لمساعدة هيئات المعونة بسعر 3.20 يورو (3.66 دولار) للجهاز الواحد.

وأعلنت منظمة الصحة العالمية، فى أحدث بياناتها أن عدد الحالات الجديدة المصابة بإيبولا ارتفع الأسبوع الماضي في البلدان الثلاثة الأكثر تضررا بغرب إفريقيا، وهى ليبيريا وسيراليون وغينيا.


وأضافت المنظمة أنه إجمالا توفي 8981 شخصًا، من بين 22495 حالة إصابة بإيبولا ظهرت في 9 دول منذ بدء انتشار المرض في كانون الأول/ديسمبر عام 2013 .



Pneumonia May Be Worsened by Acid Suppressive Therapy





Proton pump inhibitors (PPIs) are effective and generally safe medications for patients with acid-related disorders. However, this drug class has come under scrutiny in recent years because of potential adverse effects associated with long-term use.


Corleto and colleagues addressed the potential dangers of PPIs in a review published in the February 2014 issue of Current Opinion in Endocrinology, Diabetes, and Obesity.


They found that PPIs were certainly associated with hypomagnesemia. However, they noted that the evidence that PPIs may increase the risk for fracture was fairly weak. Moreover, only limited evidence suggests that PPIs may promote a higher risk for infection with Clostridium difficile. However, the risk for microscopic colitis appears elevated among patients who use PPIs, even for a short amount of time.


This review was largely dismissive of the potential for serious risks associated with the use of PPIs, but there is little doubt that PPIs remain one of the most overused of all prescribed medications.


In a study of PPI prescriptions by hospitalists, Eid and colleagues found that only 39% of these prescriptions followed published guidelines for PPI use among inpatients. This research, which was published in Internal Medicine in 2010, found that the most common erroneous indication for providing PPIs was prophylaxis against gastrointestinal tract bleeding.


Physicians in academic centers were more likely to adhere to PPI-prescribing guidelines, and an inappropriate PPI prescription in the hospital was associated with a higher chance of being prescribed a PPI, probably inappropriately as well, as an outpatient.


The current study by Bhattarai and colleagues, results which were presented at the 2014 American College of Chest Physicians Meeting, evaluates another potential risk associated with gastric acid suppression: community-acquired pneumonia.




Acid suppressors are associated with more severe community-acquired pneumonia, according to a study performed at an inner-city hospital. However, comorbidities such as diabetes and chronic obstructive pulmonary disease (COPD) could have played a role in the results.


"I looked through the literature and found there was a high association between acid suppression and ventilator-associated pneumonia," chief resident Bikash Bhattarai, MD, who is now a pulmonary fellow at the Interfaith Medical Center in Brooklyn, New York, told Medscape Medical News.


Previous research has shown that acid suppression can increase susceptibility to community-acquired pneumonia, possibly because reducing gastric acid secretion enhances colonization of the upper gastrointestinal tract with oral bacteria.


However, none of the participants in those studies were black. "We have a huge African American population, so that's what prompted me to do the study," Dr Bhattarai explained here at CHEST 2014.


His team conducted a retrospective analysis to determine whether there was also an association between acid suppression and severity of community-acquired pneumonia.


The researchers analyzed all patients with community-acquired pneumonia admitted to their inner-city hospital from 2010 to 2013. Patients who were suspected of having aspiration pneumonia or who were immunosuppressed in any way were excluded from the analysis.

In the study cohort, 86% of patients were black and 53% smoked. Although there were no fundamental differences in demographic characteristics, there was more use of acid suppression at the time of hospital admission in patients with certain comorbidities.



 Table 1. Association Between Acid Suppression and Comorbidities


Acid Suppression (n = 468), %

No Acid Suppression (n = 398), %




Diabetes mellitus



Previous stroke






Chronic kidney disease





Physicians are very comfortable prescribing acid suppression. In fact, one meeting attendee said that the proportion of patients with community-acquired pneumonia taking acid suppressors was surprisingly low (46%). However, the results of the study suggest that the agents should be used more judiciously, said Dr Bhattarai.


"Even when the patient comes to the hospital, I'm not very comfortable discontinuing the acid suppressors, and my reflex is to put them on the medication if they're not on it already.


But we shouldn't give these medications if they aren't indicated because there are risks," he said.


There was also an association between acid suppression and indicators of the severity of community-acquired pneumonia, some of which fell just short of statistical significance.


Table 2. Link Between Acid Suppression and Severity of Pneumonia


Indication of Severity

Acid Suppression (n = 468)

No Acid Suppression (n = 398)

P Value

Positive blood culture result (%)



< .001

Thrombocytopenia (%)



< .001

Radiologic pneumonia (%)




Length of hospital stay (days)




Mortality (%)









 Still, not everyone is convinced by the data. The study was observational and relatively small, and confounding factors might explain the results, according to Punginathn Dorasamy, MB ChB, professor of medicine at McMaster University in Hamilton, Ontario, Canada, who attended the presentation.

He pointed out that previous research has yielded conflicting results and, in one case, the study authors suspected that patients receiving acid suppressors had preexisting conditions that predisposed them to pneumonia.


"It's difficult to say that acid suppression is contributing to the worsening of the pneumonia. But there may be a message that in a small subset of patients, such as those with diabetes or COPD, if we are suppressing the acid, we may increase the risk of severe types of pneumonia," Dr Dorasamy told Medscape Medical News.


Dr Bhattarai and Dr Dorasamy have disclosed no relevant financial relationships.


CHEST 2014: American College of Chest Physicians Meeting. Abstract 1972042. Presented October 28, 2014.




         The study was conducted as a retrospective analysis of cases in an inner-city community hospital in New York City.


         Researchers collected data regarding patients admitted for community-acquired pneumonia between 2011 and 2013. Patients with suspected aspiration pneumonia and those with HIV infection were excluded from analysis.

         Researchers divided the overall study cohort based on patient treatment with acid suppressive therapy before hospital admission.


         The main study outcomes were the effects of acid suppression on the severity and outcomes of community-acquired pneumonia. Researchers used a regression analysis to account for other variables separating the 2 study groups.


         866 patients were included in the analysis. An estimated 48% of patients were men, and 86% were African American.

         54% of the study sample had received acid suppressive therapy.


         Demographic variables were not significantly associated with the use of acid suppressive therapy, but patients with more comorbidity, including COPD, diabetes mellitus, previous stroke, or cancer were more likely to receive acid suppressive treatment.


         Rates of positive blood culture results were higher among patients who received acid suppressive therapy vs those who did not (12% vs 5.5%, respectively). The respective rates of thrombocytopenia were 22% and 17%. Both of these differences were statistically significant.


         However, the rates of radiologic evidence of pneumonia were similar and were above 90% regardless of acid suppressive therapy.


         The average lengths of hospital stay among patients who did and did not receive acid suppressive therapy were 10.51 and 8.96 days, respectively. The respective rates of mortality were 15.1% and 11.5%. Both of these differences just missed statistical significance.




         Good evidence exists that PPIs are widely overused among inpatients. However, a review found weak evidence that PPIs may adversely affect bone health or increase the risk for infection with C difficile. PPIs do promote hypomagnesemia.


         The current study by Bhattarai and colleagues suggests that adults using acid suppressive therapy are more likely to have severe community-acquired pneumonia and experience longer lengths of hospital stay and higher rates of mortality.








Aspirin Ineffective in Preventing Cardiovascular Disease

Although cardiovascular disease is the number one cause of mortality in the developed world, the impact of cardiovascular disease from region to region can be heterogeneous. Therefore, it is important to understand trends in cardiovascular disease from a geographic and cultural perspective.
Hata and colleagues did just that in evaluating trends in cardiovascular disease and risk factors in Japan.
Their research, which was published in the September 10, 2013, issue of Circulation, demonstrated that certain risk factors, such as blood pressure control among patients with hypertension and the overall rate of smoking, improved in the general Japanese population in the 4 to 5 decades between the 1960s and 2000s. However, these positive changes were counterbalanced by a strong increase in rates of obesity, hyperlipidemia, and glucose intolerance during the same period.
Overall, these diverging trends resulted in no substantial change in the rate of myocardial infarction (MI) through the decades, although rates of mortality from stroke were reduced because of lower stroke incidence and better stroke management.
Could aspirin as primary prophylaxis help to reduce the risk for cardiovascular disease in Japan? The current study by Shimada and colleagues yields results with clear implications for the management of all adults worldwide.
A new trial shows no benefit of low-dose, once-daily aspirin in the primary prevention of cardiovascular events in patients with multiple risk factors, including hypertension, diabetes, and dyslipidemia.
No benefit was seen for the composite endpoint of nonfatal MI, nonfatal stroke, or death from cardiovascular causes. There were significant reductions in MI and in transient ischemic attack (TIA), but a significant increase in serious extracranial hemorrhage meant that the net benefit was questionable.
The overall rate of events was much lower than anticipated in this study, and it did not reach statistical significance, said study coauthor Kazuyuki Shimada, MD, Department of Cardiology, Shin-Oyama City Hospital, Tochigi, Japan. "Therefore, the possibility that aspirin does have a beneficial effect in this population cannot be excluded."
Still, the clinical importance of aspirin for primary prevention was "less than originally anticipated in this population," he concluded, and further analyses are planned to see whether they can identify patients who may benefit most from aspirin.
"Lastly, it will be interesting to see if the ongoing studies ARRIVE, ASCEND, ASPREE, and ACCEPT-D, which are assessing primary prevention in predominantly Western populations, have different outcomes to our study in Japanese patients," Dr Shimada said.
The results of the Japanese Primary Prevention Project (JPPP) were published online November 17 in JAMA to coincide with presentation here at the American Heart Association 2014 Scientific Sessions.
Primary Prevention
For the last several years, the benefits and risks associated with aspirin for primary prevention of cardiovascular events for those at moderately increased risk have been "hotly debated," Dr Shimada said. "Recently the FDA [Food and Drug Administration] cautioned against the general use of aspirin for the primary prevention of heart attacks and strokes," he noted. An FDA release on May 5 concluded that after a review of the literature, the evidence does not support the use of aspirin for primary prevention.
"In order to inform our decision making in Japan and to develop country-specific recommendations, we conducted the Japanese Primary Prevention Project study, which prospectively evaluated daily, low-dose aspirin in the primary prevention of CV [cardiovascular] events in elderly Japanese patients with cardiovascular risk factors," Dr Shimada said.
The JPPP was a multicenter, open-label, randomized, parallel-group trial. Using a Prospective Randomized Open Blinded Endpoint study design, patients with hypertension, dyslipidemia, and/or diabetes mellitus without a history of cardiovascular disease were enrolled during routine visits to their primary care provider at one of 1007 clinics in Japan between March 2005 and June 2007.
A total of 14,658 patients were randomly assigned to receive 100 mg of enteric-coated aspirin per day or no aspirin, along with continuous management of their other risk factors. Patients were to be monitored for up to 6.5 years, with last follow-up in May 2012. Study outcomes were adjudicated by an expert panel blinded to treatment assignments.
"At the time of the second interim analysis in May 2011, the independent data monitoring committee recommended that the study was to be discontinued at the next annual study assessment due to futility and to avoid unnecessary risk of adverse events," he said. At the time of study discontinuation, patients had been followed up for a median of 5.02 years (interquartile range, 4.55 - 5.33 years).
The primary outcome was a composite of death from cardiovascular causes (MI, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal MI. Secondary outcomes included those events plus TIA, angina pectoris, and atherosclerotic disease requiring surgery or intervention, as well as each individual outcome.
A total of 56 fatal events occurred in each group. Nonfatal stroke occurred in 117 patients in the aspirin group and 114 in the no-aspirin group. Nonfatal MI was seen in 20 patients taking aspirin vs 38 in the no-aspirin group, and undefined cerebrovascular events occurred in 3 patients receiving aspirin vs 5 patients not receiving aspirin.
"There was no statistically significant difference between the two groups in time to the primary end point," Dr Shimada reported. "The hazard ratio indicates that there was an insignificant 6% reduction in the risk of a primary end point event in the aspirin group vs the no-aspirin group."
Table. JPPP: Main Outcomes

End Point


No Aspirin

Hazard Ratio (95% Confidence Interval)


Five-year cumulative event rate (%)

2.77 (2.40 - 3.20)

2.96 (2.58 - 3.40)

0.94 (0.77 - 1.15)


Nonfatal MI

0.30 (0.19 - 0.47)

0.58 (0.42 - 0.81)

0.53 (0.31 - 0.91)



0.26 (0.16 - 0.42)

0.49 (0.35 - 0.69)

0.57 (0.32 - 0.99)


Extracranial hemorrhage requiring transfusion or hospitalization

0.86 (0.67 - 1.11)

0.51 (0.37 - 0.72)

1.85 (1.22 - 2.81)



The risk for a primary end point event did not differ significantly for aspirin vs no aspirin in any of the disease risk factor subgroups assessed, including hypertension vs no hypertension, dyslipidemia vs no dyslipidemia, diabetes vs no diabetes, and family history vs no family history, or by demographic factors such as age and gender.


For most secondary end points, there was no significant difference between the treatment groups. However, nonfatal MI was significantly reduced by 47% with aspirin vs no aspirin, and TIA was reduced by a significant 43%, Dr Shimada said.


"Conversely, there was a significant increase in serious extracranial hemorrhage in the aspirin group -- the hazard ratio indicates an 85% increase in such events," he said. "Therefore, any benefits of aspirin in terms of the reduced risk of nonfatal MI and TIA must be counterbalanced with consideration of the significantly increased risk of serious extracranial hemorrhage."


Finally, there was a prespecified analysis of gastrointestinal (GI) adverse events in the randomly selected population. "The results clearly indicate that aspirin is associated with an increased incidence of these GI events, the known side-effect profile of aspirin, although the study was unblinded and these were not primary or secondary analyses," he said.


Less Power, Increasing Challenge


In an accompanying editorial, J. Michael Gaziano, MD, MPH, Veterans Affairs Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, and associate editor of JAMA, and Philip Greenland, MD, Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, and senior editor of JAMA, point to the lower-than-expected event rate in this study, "leading to a study with less power to detect differences in the primary outcome than anticipated."


Aspirin primary prevention trials have "become increasingly challenging to conduct," they write. "There is wider use of a number of prevention medications such as antihypertensive agents and lipid-lowering drugs, as well as other preventive measures that collectively result in fewer events than expected, as seen in JPPP."


The findings add to the "body of evidence that helps refine the answer to the question of when aspirin should be used to prevent vascular events," they say. "Decision making involves an assessment of individual risk-to-benefit that should be discussed between clinician and patient."


In some situations the benefit of aspirin is clear, such as those at high short-term risk after an acute vascular event, or those undergoing certain vascular procedures, they add. "On the other hand, patients at very low risk of vascular events should not take aspirin for prevention of vascular events, even at low dose."


In the middle are those without overt vascular disease but risk levels approaching those with cardiovascular disease. "It remains likely that there is some level of risk of CVD [cardiovascular disease] events that would result in a positive trade-off of benefit and risk for the use of aspirin, but the precise level of risk is uncertain. This is in part because most populations studied have been at very low risk."


The editorialists also point to the ongoing ASCEND, ARRIVE, and ASPREE studies to help refine guidelines in higher-risk patients.


"Findings from these studies, with additional data about risks and other potential long-term benefits, such as reducing the risk of colorectal and other cancers, will prove helpful for clinical decision making involving the role of aspirin for primary prevention," Dr Gaziano and Dr Greenland conclude.


End of the Road?


At the meeting here, Dorairaj Prabhakaran, DM, vice president and professor of epidemiology, Public Health Foundation of India, and professor of epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom, was the invited discussant for this trial. He considered the question of whether these findings spell the "end of the road for aspirin in primary prevention."


Among the reasons the trial was negative were the lack of power because of early termination, he said, and the fact that aspirin on a background of widespread statin use may make it difficult to show a benefit.


"Benefit is very unlikely in low-risk populations such as those with less than 1% events per year," Dr Prabhakaran said. "There could be a role in special groups, particularly younger populations that are not being evaluated well from low-/middle-income countries like India, where the risk of coronary artery disease is extremely high."


Risk scores are needed for these countries to identify high-risk people, he added, and "we also await the results of other studies in primary prevention," such as the TIPS-2 trial in India that combines a "polypill" with aspirin, he noted.


If risk is less than 10%, benefit is unlikely, but there is a "gray area" between 10% and 20% where benefit may yet be seen with aspirin for primary prevention, he said (J Am Coll Cardiol. 2014;64:319-327).

He quoted Sir Richard Doll, who once said, "Death is inevitable, but premature death is not."


"In reducing premature death, aspirin is the most inexpensive option and we should pursue with vigor in identifying individuals and populations who may benefit," Dr Prabhakaran concluded.


During a discussion after the presentation, Christopher Cannon, MD, Harvard Medical School, pointed out that in his practice, many patients arrive having already started aspirin therapy on their own, "whereas we're seeing there's an active decision of benefit and risk that needs to be taken.

"It's a serious decision whether to start aspirin, so this is a terrific reminder that we really need to calculate based on risk and see could this be of benefit, or would there be more harm?" he added.


The JPPP was sponsored by the Japanese Ministry of Health, Labor, and Welfare and the Waksman Foundation of Japan. Enteric-coated 100-mg aspirin tablets were provided free of charge by Bayer Yakuhin. Dr Ikeda discloses receiving fees for medical advice from AstraZeneca, Bayer, Daiichi Sankyo, GlaxoSmithKline, and sanofi-aventis. Disclosures for coauthors appear in the publication.


JAMA. Published online November 17, 2014. Abstract Editorial

American Heart Association (AHA) 2014 Scientific Sessions. Presented November 17, 2014.



         The study was designed as an open-label clinical trial. Participants were recruited from 1007 primary care offices in Japan between 2005 and 2007.


         Patients eligible for study participation were between 60 and 85 years old and had no history of cardiovascular events. However, all participants had hypertension, hyperlipidemia, or diabetes.


         Participants were randomly assigned to receive aspirin 100 mg daily or no aspirin. Their ongoing treatment was otherwise unchanged, save for the fact that they were prohibited from using other antiplatelet or anticoagulant drugs.


         Study outcomes were reported by the primary care clinics to the central research team. The primary study outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal MI. Researchers also followed rates of TIA and angina pectoris. Finally, rates of adverse events such as bleeding and GI complications were measured.


         The study analysis evaluated the efficacy of aspirin in the context of participants' total cardiovascular risk profile.


         The study was complicated by a lower rate of incident cardiovascular events. By 2011, only 290 primary end point events had occurred among the 14,658 patients enrolled in the study, although researchers had increased enrollment in their first interim analysis.


         The median age of the 14,658 study participants was 70 years. An estimated 58% of the study cohort consisted of women, 85% of participants had hypertension, 72% had hyperlipidemia, and 34% had diabetes. Approximately 13% of the cohort consisted of current smokers.


         Adherence to aspirin therapy was fair overall, with values of 88.9% at year 1 of the study and 76.0% in year 5.


         Nearly 10% of patients in the control group began aspirin therapy by year 5, and 10% of patients in both cohorts received other antiplatelet or anticoagulant medications by year 5.


         The study steering committee prematurely stopped the research after a median follow-up period of 5.02 years because of a lack of efficacy of aspirin in preventing the primary study outcome.


         At 5 years, the respective rates of incident cardiovascular outcomes in the aspirin and no-aspirin groups were 2.77% and 2.96%. The estimated hazard ratio (HR) for the primary outcome in comparing the aspirin group vs the no-aspirin group was 0.94 (95% CI, 0.77 - 1.15).


         Subgroup analysis based on age, gender, and the presence of different cardiovascular risk factors failed to yield any significant advantage for aspirin therapy.


         Adding TIA and angina pectoris to the main composite outcome also failed to demonstrate any significant benefit for aspirin therapy.


         The overall mortality rate was similar in the aspirin and no-aspirin cohorts.


         In an analysis focused on individual event outcomes, aspirin was associated with a significant reduction in the risks for nonfatal MI (HR, 0.53; 95% CI, 0.31 - 0.91) and TIA (HR, 0.57; 95% CI, 0.33 - 0.99).


         Aspirin was also associated with a higher risk for extracranial hemorrhage requiring transfusion or hospitalization (HR, 1.85; 95% CI, 1.22 - 2.81). Aspirin treatment was associated with higher rates of abdominal pain, heartburn, and gastroduodenal ulcer.



         A previous study by Hata and colleagues of trends in cardiovascular disease in Japan from the 1960s to the 2000s demonstrated improved hypertension control and lower rates of smoking, which was counterbalanced by higher rates of obesity, glucose intolerance, and hyperlipidemia. Overall, the risk for MI remained stable during this period, although the risk for stroke improved.


         The current study by Shimada and colleagues demonstrates that aspirin may be ineffective as primary cardiovascular prevention among older adults at elevated risk for cardiovascular disease. Aspirin was effective in preventing nonfatal MI and TIA but did not improve mortality outcomes and promoted a higher risk of serious extracranial bleeding.


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