SUMMARY AND COMMENT

More About Blood Pressure in the Very Old

October 30, 2008 | Allan S. Brett, MD

Once again, a study suggests an inverse relation between blood pressure and mortality in the oldest segment of the population.

Reviewing: Molander L et al. J Am Geriatr Soc 2008 Oct 56:1853

Free Full-Text Article

Feature Statin Side Effects — Targets of Ongoing Research In particular, researchers are looking at cognitive and musculoskeletal effects of statins. Although statins generally are well tolerated, many clinicians believe that, in practice, statin-related side effects occur more commonly than was reported in randomized trials. Muscle symptoms, the most well-known statin side effect, can occur without elevated creatine kinase (CK) levels. Indeed, one study demonstrated reversible pathologic abnormalities on muscle biopsies in patients with normal CK levels who developed muscle pain or weakness while taking statins (JW Nov 1 2002). Recently, researchers identified a common variant of a gene on chromosome 12 that predisposes patients to statin myopathy.1 Determining whether a statin user’s myalgias are related to the drug often is difficult. Thus, we would benefit by knowing whether statin users, as a group, experience muscle symptoms in excess of the background prevalence. In a recent study, in which researchers used the nationally representative NHANES database and excluded people with known arthritis, 22% of statin users and 17% of nonusers reported musculoskeletal pain. In a multivariable analysis, statin users exhibited significantly increased odds for musculoskeletal pain compared with nonusers (odds ratio, 1.5, after adjustment for many potentially confounding variables).2 Although this cross-sectional analysis has limitations, it suggests that statin-associated muscular symptoms are not rare. A point of controversy is whether statins cause cognitive problems in some people. This issue made national headlines in February 2008, when a Wall Street Journal article described patients who had developed problems with memory and other cognitive skills while taking statins. The article included testimonials by academic physicians and an affected patient.3 Other experts have expressed concerns that these reports exaggerate statin risks and that negative publicity about statins will frighten patients unnecessarily. Yet another concern about statins and cognition was raised in a recently published study. Canadian researchers used a national database to conduct a retrospective analysis of nearly 300,000 patients (age, 65) who had undergone elective surgery. Patients who had been prescribed statins during the previous 90 days had a significantly higher risk for developing postoperative delirium than did statin nonusers (OR, 1.3 after adjustment for many potential confounders). The database did not indicate when statin users last took statin drugs before surgery, ascertainment of delirium cases was incomplete, and hidden confounding that was not captured by the database is possible. Intriguingly, no other class of cardiovascular drugs was associated with postoperative delirium. The authors speculate that altered cerebral blood flow, resulting from the effects of statins on vascular smooth muscle, could be one mechanism for statin-induced postoperative delirium.4 If this theory is borne out, it would compete with other data that suggest an association between perioperative statin therapy and lower postoperative mortality.5 The beneficial effects of statins in high-risk patient populations are indisputable. However, these drugs increasingly are being prescribed to asymptomatic people on the basis of somewhat arbitrary serum lipid thresholds, without regard to overall cardiovascular risk. Thus, gathering more information about potential adverse effects is imperative. One noteworthy effort comes from the University of California at San Diego, where researchers have conducted an NIH-funded randomized placebo-controlled trial to gather detailed information about statin side effects. The study focused particularly on statins’ effects on cognition and behavior but also tracked other adverse effects.6 Results should be available soon. In addition, the same group currently is conducting an observational study called the Statin Effects Study. — Allan S. Brett, MD Published in Journal Watch General Medicine October 28, 2008 Citation(s): 1. Link E et al. SLCO1B1 variants and statin-induced myopathy — A genomewide study. N Engl J Med 2008 Aug 21; 359:789. (http://dx.doi.org/10.1056/NEJMoa0801936) Original article (Subscription may be required) Medline abstract (Free) 2. Buettner C et al. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med 2008 Aug; 23:1182. (http://dx.doi.org/10.1007/s11606-008-0636-7) Medline abstract (Free) 3. Beck M. Can a drug that helps hearts be harmful to the brain? Wall Street Journal 2008 Feb 12. (http://online.wsj.com/article/SB120277403869360595.html) 4. Redelmeier DA et al. Delirium after elective surgery among elderly patients taking statins. CMAJ 2008 Sep 23; 179:645. (http://dx.doi.org/10.1503/cmaj.080443) Original article (Subscription may be required) Medline abstract (Free) 5. Hindler K et al. Improved postoperative outcomes associated with preoperative statin therapy. Anesthesiology 2006 Dec; 105:1260. Medline abstract (Free) 6. Golomb BA et al. Conceptual foundations of the UCSD Statin Study: A randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry. Arch Intern Med 2004 Jan 26; 164:153. Original article (Subscription may be required) Medline abstract (Free)

Beta-blocker induced heart rate reduction ‘harmful in hypertension’

24 October 2008

MedWire News: Slower heart rates are associated with an increased risk for cardiovascular (CV) events and death in patients with hypertension being treated with beta blockers, a meta-analysis of randomized controlled trials (RCTs) has shown.

The finding was unexpected and contrasts with the effect of beta blockers in patients with myocardial infarction (MI) or heart failure, in whom pharmacological heart-rate reduction is known to be beneficial.

The study, by Frank Messerli’s group at St Luke’s Roosevelt Hospital and Columbia University, New York, USA, aimed to evaluate the role of heart-rate reduction with beta blockers on the risk for CV events in patients with hypertension.
“Given that resting heart rate is a risk factor, slowing it should have beneficial effects,” the authors remark.

They searched the literature for RCTs that evaluated beta blockers as first-line therapy for hypertension and featured 1-year follow-up plus data on heart rate. Nine trials were eligible; they included 34,096 patients randomized to beta-blockers (mainly atenolol), 30,139 taking other antihypertensive drugs, and 3,987 taking placebo.

Unexpectedly, Messerli et al found that after 1 year of beta-blocker therapy heart rates inversely correlated with all-cause mortality (p<0.0001), cardiovascular mortality (p<0.0001), MI (p<0.0001), stroke (p=0.06), and heart failure (p<0.0001).

The authors say the most likely explanation for their findings is that pharmacologically induced bradycardia leads to dyssynchrony between outgoing and reflected pulse wave, thereby increasing central aortic pressure and the hemodynamic burden to the target organs.

They conclude: “In contrast to patients with MI and heart failure, beta-blocker– associated reduction in heart rate increased the risk for cardiovascular events and death for hypertensive patients.”

In an accompanying editorial Norman Kaplan (University of Texas Southwestern Medical Center, Dallas, TX) says the new data add weight to the argument that beta blockers are not appropriate therapy for primary uncomplicated hypertension.

“With this addition to the evidence, beta blockers will surely remain indicated for heart failure, for after MI, and for tachyarrhythmias, but no longer for hypertension in the absence of these compelling indications,” he observes.

J Am Coll Cardiol 2008; 52: 1482–1489

Vitamin B Supplementation and Progression of Alzheimer Disease

Dietary supplementation with folate, vitamin B₆, and vitamin B₁₂ did not slow progression of dementia at 18 months.

Statins and Cognitive Impairment

Findings from a prospective observational study support the thesis that statin use may protect against the eventual development of dementia.

Research findings regarding the posited effects of statins on declining cognitive function are inconsistent. To explore statins’ associations with dementia and with cognitive impairment, no dementia (CIND), investigators analyzed data from a population-based cohort of participants 60 and older in the Sacramento Area Latino Study on Aging (SALSA).

A total of 1674 participants had no dementia or CIND at baseline. Of these, 452 (27%) used statins at baseline or during the 5-year follow-up period; 43 participants who used other, nonstatin lipid-lowering therapies were classified with the statin nonusers. Of the statin users, 58% took them for 2 study years. Although statin users and nonusers were comparable with respect to many baseline characteristics, a significantly higher percentage of statin users than nonusers had a history of diabetes. During follow-up, 130 participants developed dementia or CIND. In unadjusted analysis, statin use was associated with a 43% decrease in the rate of dementia or CIND, compared with statin nonuse. In a Cox proportional hazards-adjusted model, the rate of dementia or CIND was 44% lower among statin users than among nonusers.

Comment: In this predominantly Mexican American population, statin use was associated with a lower rate of dementia or cognitive impairment without dementia than statin nonuse. However, randomized trials of statins for primary prevention of any kind of dementia or cognitive decline in different populations are needed before statins are routinely deployed to prevent cognitive decline.

— Joel M. Gore, MD

Published in Journal Watch Cardiology July 28, 2008

Citation(s):

Cramer C et al. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008 Jul 29; 71:344.

• Original article (Subscription may be required)
• Medline abstract (Free)

10 microgram vitamineD is gelijk aan 400 I.U.
October 14, 2008 — The American Academy of Pediatrics (AAP) has issued updated guidelines for vitamin D intake in infants, children, and teens to prevent rickets and vitamin D deficiency. The new recommendations were posted in the October 13 Early Release issue and will be published in the November 5 print issue of Pediatrics.

The recommendations were also presented at the American Academy of Pediatrics 2008 National Conference and Exhibition in Boston, Massachusetts.

The updated guidelines replace a 2003 AAP clinical report, which recommended a daily intake of 200 IU per day of vitamin D for all infants, from the first 2 months after birth, as well as for children and adolescents. The new recommendations call for a daily intake of 400 IU per day of vitamin D for all infants, children, and adolescents beginning in the first few days of life.

"Rickets attributable to vitamin D deficiency is known to be a condition that is preventable with adequate nutritional intake of vitamin D," write Carol L. Wagner, MD, Frank R. Greer, MD, and the AAP Section on Breastfeeding and Committee on Nutrition. "Despite this knowledge, cases of rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continue to be reported in the United States and other Western countries, particularly with exclusively breastfed infants and infants with darker skin pigmentation. Rickets, however, is not limited to infancy and early childhood, as evidenced by cases of rickets caused by nutritional vitamin D deficiency being reported in adolescents."

The primary natural source of vitamin D is from skin synthesis from cholesterol after exposure to UVB light. Natural dietary sources of vitamin D are limited, and the amount of sunshine exposure sufficient for the cutaneous synthesis of vitamin D is not easily determined for a given individual. Furthermore, that amount of sunshine exposure may increase the risk for skin cancer. Therefore, the AAP has revised its 2003 recommendations to ensure adequate vitamin D status to include all infants, including those who are exclusively breast-fed, as well as older children and adolescents.

All infants and children, including adolescents, should have a minimal daily intake of 400 IU of vitamin D beginning soon after birth, according to these revised guidelines. The current recommendation for healthy infants, children, and adolescents is based on findings from new clinical trials as well as on the historical precedent of safely administering 400 IU of vitamin D per day in the pediatric and adolescent populations. Furthermore, ingestion of 400 IU of vitamin D daily appears to treat as well as to prevent rickets.

Publication Logo (Reuters)
Obesity May Raise Risk of Progression to Permanent Atrial Fibrillation

Information from Industry
Atrial Fibrillation Condition Site
Explore the burden of AF and sinus rhythm as a treatment target.

NEW YORK (Reuters Health) Oct 10 - New research suggests that obesity not only increases the risk of first atrial fibrillation, it also increases the odds that paroxysmal atrial fibrillation will become permanent.

"This study extends our understanding of the relationship between obesity/left atrial size and atrial fibrillation. Specifically, there was a graded risk relationship between body mass index and progression from paroxysmal to permanent atrial fibrillation, and larger left atrial size augmented the risk of such progression," Dr. Teresa S. M. Tsang and associates write.

The study, which is reported in the European Heart Journal for September, involved 3248 patients in Olmsted County, Minnesota, who were diagnosed with paroxysmal atrial fibrillation between 1980 and 2000, and were followed through 2006.

During a median of 5.1 years, 557 subjects (17%) progressed to permanent atrial fibrillation, Dr. Tsang, from the Mayo Clinic in Rochester, Minnesota, and colleagues report.

On multivariate analysis, BMI was an independent predictor of progression to permanent atrial fibrillation. Relative to normal BMI, obesity and severe obesity increased the odds of progression by 54% (p = 0.0004) and 87% (p < 0.0001), respectively.

Echocardiographic assessment, which was performed in a subset of 744 patients, indicated that left atrial volume did not attenuate the association between BMI and progression to permanent atrial fibrillation.

"Studies of weight reduction, and of reversal of left atrial enlargement, may provide insight as to whether these interventions may lower the risk for the development of first atrial fibrillation, and reduce or delay the progression from paroxysmal to permanent atrial fibrillation," the research team suggests.

Eur Heart J 2008;29:2227-2233.

Medscape from WebMD
www.medscape.com

What Happened to the Polypill?

Geoff Watts

BMJ. 2008;337(1822) ©2008 BMJ Publishing Group
Posted 10/09/2008

A single pill to prevent cardiovascular disease sounds like a perfect solution, but little progress has been made since the idea was first suggested. Geoff Watts investigates why.

When Nicholas Wald, head of London's Wolfson Institute of Preventive Medicine, and his colleague Malcolm Law published their case for the prevention of heart disease using a "polypill",[1] an accompanying editorial described it as "one of the boldest claims for a new intervention."[2] The substance of the claim was that, if taken by everyone with established cardiovascular disease and -- most importantly -- all those aged 55 or over, the polypill could reduce rates of heart attack and stroke by more than 80%.

Now, more than five years later, you might imagine that a clutch of research groups would be eagerly competing to test this innovative suggestion. Not so.

As conceived by Professors Wald and Law, the polypill comprised a statin, aspirin, three types of blood pressure lowering drug, and folic acid -- intended to lower serum homocysteine concentrations. The logic was that most people in Western society are at raised risk, that cardiovascular disease is consequently common, and that the drugs to treat it are effective and safe. "No other preventive method," they wrote, "would have so great an impact on public health in the Western world." Since that time, Professor Wald says, nothing has happened to change his mind.

The few trials that have been planned lack the scope and ambition of Professor Wald's original proposal. One, for example, is being organised by Anthony Rodgers of the University of Auckland's clinical trials research unit. His pilot study is recruiting 400 participants from New Zealand, Brazil, India, and elsewhere for a 12 week placebo controlled trial of a pill containing blood pressure and cholesterol lowering drugs together with aspirin.[3] But all his participants are selected because they are at increased risk of heart attack or stroke; they are not intended to reflect a section of the population at large.

Another study is being led by Valentin Fuster of Mount Sinai Hospital in New York. He is also the scientific director of Spain's National Centre for Cardiovascular Research, the body through which the trial is being organised. His polypill variant comprises aspirin, a statin, an angiotensin converting enzyme inhibitor, and a beta blocker. But all the participants have had a myocardial infarction, and his intention is to learn whether having to swallow only a single pill will improve compliance. At present, he says, only one third to half of patients take all the drugs necessary to prevent a second heart attack.

Professor Fuster is particularly keen to explore the relevance and affordability of a polypill in low income countries. One of his hopes when full trials start -- subject to US Food and Drug Administration approval -- is to show how secondary prevention of heart disease can be made available in the developing world.
Primary Concerns

Professor Wald knows of no plans to run a trial of the polypill on a general healthy population. So, mindful of its potential impact on public health, why the reluctance?

It is likely that Professor Fuster speaks for others besides himself when he explains why his study is limited to secondary prevention. "This is not the solution for primary prevention," he says. "Primary prevention requires education of the public. As a priority this is much more important than any polypill."

It's a view that Professor Wald has been confronting ever since he published his BMJ paper. "Yes, in an ideal world our saturated fat intake would be lower and we'd exercise more, and we'd have less salt and sugar in our diet. But this is not going to happen tomorrow." He is puzzled that people seem to regard these strategies as mutually exclusive. "It's a mistake to think that when you can do things two ways it has to be one or the other."

The polypill concept is also accused of "medicalising" whole populations. "Quite the reverse," Professor Wald insists. "If you test people to see if they've got high blood pressure or high cholesterol, give them a disease label, and then have them come back regularly to find out if things have changed, you've created a patient." This, he argues, is the real medicalisation -- not universal access to a pill.

Does he sense a moral objection of some kind to the use of drugs rather than lifestyle changes? He does. "There's an unstated view that if you're not a patient, taking pills may be regarded as a weakness. Once you're a patient you're relieved of that burden." Such a view, he thinks, is unreasonable. "Is getting vaccinated a moral weakness?"

The only people currently contemplating a trial in a population defined by age seem to be Professor Wald and his colleagues. With a polypill developed by the Indian generics company Cipla he hopes to set up a project in the developing world. This choice of location would be partly to minimise cost, but also because guidelines on cardiovascular screening in the UK would require participants in the placebo group with problems identified by baseline tests to get some treatment, so making it harder to show the polypill's effects.

At present no polypill formulation has been licensed in Europe or America. But if and when a combined pill for treating hypercholesterolaemia and hypertension as part of secondary prevention wins regulatory approval, new possibilities will open up. "Once a polypill is on the market, doctors can prescribe it as they see fit." It's this, Professor Wald suspects, that will eventually lead to a wider exploration of its benefits.
References

1. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003;326:1419-24.
2. Rodgers A. A cure for cardiovascular disease? BMJ 2003;326:1407-8.
3. University of Auckland Clinical Trials Research Unit. PILL pilot: programme to improve life and longevity. 2008. www.ctru.auckland.ac.nz/content/view/37/35/.


Geoff Watts, freelance journalist, London, geoff@scileg.freeserve.co.uk

Dislcosure: None declared.

October 7, 2008 — Proton-pump inhibitors (PPIs) should be the mainstay of treatment and prevention of gastrointestinal ulcers and bleeding in patients on antiplatelet therapy who are at increased risk for the gastrointestinal (GI) complications, according to an "expert consensus document" developed by the American College of Cardiology, American Heart Association, and American College of Gastroenterology and published online October 3, 2008 [1].

CMAJ • August 12, 2008; 179 (4). doi:10.1503/cmaj.071330.
© 2008 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
Research
Use of proton pump inhibitors and risk of osteoporosis-related fractures
Laura E. Targownik, MD MSHS, Lisa M. Lix, PhD, Colleen J. Metge, PhD, Heather J. Prior, MSc, Stella Leung, MSc and William D. Leslie, MD

From the Departments of Gastroenterology (Targownik) and General Internal Medicine (Leslie), Division of Internal Medicine, the Department of Radiology (Leslie), Division of Nuclear Medicine, the Faculty of Pharmacy (Metge), and the Manitoba Centre for Health Policy, Department of Community Health Sciences, Faculty of Medicine (Targownik, Lix, Metge, Prior, Leung), University of Manitoba, Winnipeg, Man.

Correspondence to: Dr. William D. Leslie, C5121 St. Boniface Hospital, 409 Taché Ave., Winnipeg MB R2H 2A6; bleslie@sbgh.mb.ca

Background: The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures.

Methods: We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years.

Results: We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16–3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02–2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68–12.29, p = 0.002).

Interpretation: Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.


Related Articles

Highlights
Can. Med. Assoc. J. 2008 179: 297. [Full Text] [PDF]

Dans ce numéro
Can. Med. Assoc. J. 2008 179: 299. [Full Text] [PDF]

Proton pump inhibitors: balancing the benefits and potential fracture risks
J. Brent Richards, MD and David Goltzman, MD
Can. Med. Assoc. J. 2008 179: 306-307. [Full Text] [PDF]

Perspective NEJM
PreviousPrevious
Volume 359:1426-1427 October 2, 2008 Number 14
NextNext

The Statins in Preventive Cardiology
Daniel Steinberg, M.D., Ph.D.


Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.



- PubMed Citation
The discovery of the statins by Akira Endo and colleagues in 1976 opened the door to a new era in preventive cardiology.1 The importance of this discovery was recently underscored by Endo's receipt of the 2008 Albert Lasker Clinical Medical Research Award. By inhibiting the biosynthesis of endogenous cholesterol, the statin drugs lower elevated blood cholesterol levels much more effectively than any of the dietary or drug regimens that were available before Endo's discovery. Moreover, they have proved to be remarkably free of serious side effects.

The hypothesis that elevated blood cholesterol levels represent an important cause of atherosclerosis and . . . [Full Text of this Article]


Source Information

Dr. Steinberg is a professor emeritus, Division of Endocrinology and Metabolism, University of California, San Diego, School of Medicine, La Jolla.

Medscape from WebMD
www.medscape.com

To Print: Click your browser's PRINT button.
NOTE: To view the article with Web enhancements, go to:
http://www.medscape.com/viewarticle/581256



Publication Logo
Late-Life Depression May Have a Vascular Etiology

Reuters Health Information 2008. © 2008 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.

NEW YORK (Reuters Health) Oct 02 - Vascular depression is a subtype of late-life depression, characterized by deep white matter lesions evident on MRI, investigators report in the September 15th issue of Biological Psychiatry.

To evaluate features associated with late-life vascular depression, Dr. Joel R. Sneed, at Columbia University in New York, and his associates analyzed data from two clinical trials: the prospective Neurocognitive Outcomes of Depression in the Elderly (NCODE) study (367 subjects age 60 or older) and the Old-Old study, an 8-week study that compared the antidepressant citalopram with placebo in 174 subjects age 75 or older.

Their analyses showed that in both cohorts there were two classes of subjects, with samples approximately evenly split between the two classes. Those classified as vascular depression scored high for deep white matter and subcortical gray matter lesions, late-onset depression, and executive dysfunction. Nonvascular depression was associated with low scores for each factor.

Across both cohorts, deep white matter lesions had perfect sensitivity (1.00) and near perfect specificity (0.95) for vascular depression, the investigators report. Corresponding sensitivity and specificity were 0.61 and 0.77 for subcortical grey matter lesions, 0.33 and 0.84 for executive dysfunction, and 0.69 and 0.54 for late-onset depression.

Dr. Sneed's group notes that "patients with deep white matter hyperintensity burden might also present with cognitive deficits, falls, gait disturbance, and urinary incontinence without depressed mood or anhedonia. Thus, vascular depression may be viewed as part of a larger category of cerebral white matter lesion syndrome."

The researchers therefore concluded that "while deep white matter lesion burden is necessary to receive a diagnosis of vascular depression, our confidence in the accuracy of the classification increases with the presence of additional indicators."

Biol Psychiatry 2008;64:491-497.

Atrial Fibrillation Tied to Cognitive Impairment in Patients Without Stroke

NEW YORK (Reuters Health) Sept 26 - Even in the absence of clinical stroke, atrial fibrillation (AF) is associated with impaired cognitive function and reduced hippocampal volume, according to findings from the German Atrial Fibrillation Competence Network (AFNET) study.
"AF leads to a hypercoagulatory state that could give rise to subclinical cerebral embolism," Dr. Stefan Knecht and colleagues note in the European Heart Journal for September. "Whether AF also increases the risk of cognitive decline and dementia independently of stroke is unclear."
The research team at the University of Munster examined this question in a cohort of 87 patients with AF "considerably younger than those in previous studies," and a comparator group of 446 individuals without AF matched by birth date (ages 37-84 years).
Individuals with depression, dementia, or a history of stroke were excluded and high-field MRI of the brain was used to rule out covert brain infarction.
Participants underwent in-depth neurocognitive evaluation. After controlling for age, gender, education, and other risk factors, AF was significantly and independently associated with worse performance in tasks of learning, memory, attention, and executive functions (p < 0.01 for each).
AF was also significantly and independently associated with hippocampal atrophy, but not with total brain volume or white matter hyperintensities.
According to the investigators, "a comparable load of white matter lesions in individuals with and without AF suggests that AF does not damage the brain by small vessel pathology but by other mechanisms -- possibly microembolism," or by abnormal hemostasis, endothelial damage, platelet dysfunction, or low cardiac output.
"Whether novel antithrombotic or rhythm-control treatments of AF can prevent cognitive decline should be studied in controlled trials," the team concludes.
Eur Heart J 2008;29:2125-2132.