Wishing you good health and lots of NSR,
Hans

I spent most of the day before downloading the book flat on my back because if I got up, my heart would start to fibrillate. I had many suicidal thoughts that day since I no longer had a life. Why does the medical establishment not know about this research? It could have saved me years of ill health and depression. Four days is perhaps too soon to say my problems are all gone but I certainly now have a handle on how to get control of my life.

LG, CANADA

Editor: I am pleased to hear that resolving your GERD made your afib disappear. You might possibly eliminate the irregular beats too by supplementing with potassium.

You are absolutely right that the medical establishment is sadly lacking when it comes to treating afib .... this is why I began www.afibbers.org

ABSTRACTS

MODENA, ITALY. Major disasters have been associated with a 5-fold increase in sudden cardiac deaths caused by ventricular arrhythmias. There is also evidence that everyday stress, such as driving and public speaking, can produce ventricular ectopy (PVCs) and runs of ventricular tachycardia. Researchers at the University of Modena now report that stress also affects the spontaneous conversion and recurrence of lone atrial fibrillation.

Their study included 116 patients who had experienced a first afib episode. The average age of the patients was 54 years and 30% of them were female. The afib group was compared with an age- and gender-matched group of volunteers who did not have afib. None of the patients were on beta-blockers, calcium channel blockers or antiarrhythmics.

The researchers found a significantly higher proportion of type A individuals among the afibbers than among the controls (20% versus 9%). High scorers on the type A scale were classified as hard-driving, fast-moving, and work-oriented individuals who frequently became impatient, irritable and annoyed. Recent exposure to acute life stress (death of a spouse, divorce, jail term, retirement, Christmas, etc) was found to be significantly more common among afibbers than among controls. Afibbers were also more likely to be high consumers of espresso coffee than were controls. A body mass index (BMI) greater than 27 was also more prevalent among afibbers than among controls. No differences in alcohol consumption, income, education, and smoking were observed between the two groups.

Spontaneous conversion of afib to normal sinus rhythm within 48 hours was observed in 72 patients (63%). Afibbers with a high BMI were less likely to convert spontaneously (they also tended to have enlarged atria) as were afibbers who had a high coffee consumption. On the other hand, afibbers who had a high score on the acute life stress scale, or exhibited distinct type A personality traits were more likely to convert spontaneously than were afibbers without these characteristics.

Recurrence of afib within 3 months of conversion was significantly less common in patients whose initial episode was related to stress than in those who had scored low on the acute life stress scale. None of the other variables affected the risk of recurrence.

The researchers speculate that the positive association between high scores on the acute life stress and type A personality scales and the likelihood of spontaneous conversion is probably due to the fact that in these types of afibbers the episode was induced by an exaggerated cardiovascular reactivity (likely over-stimulation of the sympathetic nervous system) of relatively short duration.
Mattioli, AV, et al. The relationship between personality, socio-economic factors, acute life stress and the development, spontaneous conversion and recurrences of acute lone atrial fibrillation. Europace, Vol. 7, May 2005, pp. 211-20

Editor's comment: These findings are most interesting, but it would have been helpful and perhaps more illuminating if the investigators had distinguished between adrenergic, vagal and mixed afibbers in their study.

ZWOLLE, THE NETHERLANDS. Dutch researchers have released the results of a study designed to determine the association between post-ablation left atrial size and the medium-term success of PVIs. Their study involved 105 afibbers (70% male) with an average age of 52 years (range of 27-75 years). The patients had endured afib for an average 6 years (1-11 years) with 49.5% having the paroxysmal form and 50.5% the persistent form. Only 6% had underlying structural heart disease, but 26% had hypertension.

The patients underwent a PVI using the circumferential anatomical method (Pappone method). Average procedure time and fluoroscopy time were 211 minutes and 57 minutes respectively. Twenty-two per cent of the ablatees experienced recurrent afib episodes 3 to 6 months after the initial procedure and underwent a second procedure (22% repeat rate). The patients were followed for an average of 14.6 months (6-24 months). At the last follow-up 86.5% of paroxysmal afibbers and 77% of persistent afibbers were still in normal sinus rhythm. However, 34% of afibbers in sinus rhythm needed antiarrhythmic drugs to maintain sinus rhythm. Thus the overall full success rate (no afib, no drugs) was 54%.

The researchers measured left atrium diameter (PSLAX view) before and 6 months after the ablation. They found that the average LA diameter decreased from 40.5 to 37.5 mm in successfully treated paroxysmal afibbers and noted a similar decrease in successfully treated persistent afibbers (from 44.0 to 40.0 mm). In contrast, patients who reverted to afib experienced an increase in LA diameter from an average 45 mm to 49 mm. (Editor's note: Unsuccessfully ablated afibbers would seem to have had an enlarged LA even prior to the ablation).

The researchers also found that patients with an elevated troponin T level (average 1.6 microgram/L) 16 hours after the ablation were more likely to be in sinus rhythm at long-term follow-up than were those with lower levels (average 0.87 mcg/L). Troponin T level is an indicator of the extent of damage done to the heart during the ablation and the normal range is 0-0.5 mcg/L. These findings support the contention that the more aggressive an ablation is the greater the chance of success. The Dutch researchers conclude that elevated troponin T level 16 hours post-ablation and a reduction in LA diameter 6 months after the procedure are both predictors of a successful outcome.
Beukema, WP, et al. Successful radiofrequency ablation in patients with previous atrial fibrillation results in a significant decrease in left atrial size. Circulation, Vol. 112, October 4, 2005, pp. 2089-95

Editor's comment: It is interesting to compare some of the above findings with those of the LAF Survey-9. The average age at ablation in the Dutch study was 52 years (27-75 years) compared to 55 years (27-85 years) in LAFS-9. Six per cent of participants in the Dutch study had underlying heart disease versus 7% in LAFS-9. Thirty per cent of ablatees in the Dutch study were female versus 26% in LAFS-9. Thus, the two groups would seem to be quite comparable. Success rates compared as follows:

-	Dutch Study	LAFS-9 Average	LAFS-9 "Top 9"
Full success (NSR, no drugs)	54%	41%	62%
Partial success (NSR, antiarrhythmics)	29%	17%	14%
Failure (recurrent afib)	17%	42%	24%
Repeat rate	22%	30%	20%

It is interesting to note that 16% of the patients still on antiarrhythmics were taking amiodarone thus partially accounting for the quite low failure rate in the Dutch study.

COPENHAGEN, DENMARK. Several studies and indeed our own LAF surveys have observed that many afibbers experience an increase in heart rate after a pulmonary vein isolation (PVI) procedure. Electrophysiologists at the Danish Heart Centre now confirm these observations in a study involving 62 patients with paroxysmal or persistent afib. The average age of the patients was 55 years; 29% were women and 63% had hypertension or associated cardiovascular disease. The patients were divided into two groups with one group of 37 undergoing segmental PVI (Haissaguerre method) and the remaining 25 undergoing circumferential PVI (Pappone method). A Lasso catheter was used for mapping in the segmental group, while the CARTO system was used in the circumferential group.

Successful isolation of the pulmonary veins was achieved in 97% of cases; however, a repeat ablation was required in 72% of patients having the circumferential procedure and in 73% of patients in the segmental group. A substantial number of patients (55%) required ablation in areas other than the pulmonary veins with isolation of the superior vena cava (right atrium) being the most common extra procedure (required by 26 patients). The procedure time for the segmental method was somewhat longer than for the circumferential method (166 versus 138 minutes). The procedure times for the second ablations were somewhat shorter at 115 and 99 minutes respectively. During a follow-up of 8.8 months, 35 of the 62 patients (56%) experienced recurrent afib corresponding to an overall success rate of 44%. At the 12-month follow-up point 29% of the study participants were still on antiarrhythmic drugs.

The researchers observed a significant increase in the average heart rate (in sinus rhythm) of the ablatees. One month after the ablation the average rate had increased from 58 bpm at baseline to 67 bpm and further increased to 71 bpm after 3 months; at the final measuring point 12 months after the ablation, the average heart rate was still 70 bpm. Three patients had mean heart rates of 99 bpm going as high as 140 bpm and had to be prescribed a calcium channel blocker and digoxin to reduce their heart rate to a comfortable level. The researchers noted that those patients who did not experience a recurrence of afib had a significantly greater increase in heart rate than did those whose ablations were unsuccessful (13 bpm versus 6 bpm).

Other electrophysiologists have observed increases in heart rate after PVIs, but in most cases these have been transient. The Danish researchers conclude that the increases may not be transient and that up to 5% of ablatees may need long-term medication to control symptoms associated with the uncomfortably high heart rate. They suggest that the reason for the heart rate increase is that they used deeper lesions resulting in a more extensive destruction of vagal nerve fibers and thus partial elimination of the heart's built-in slowdown mechanism. They recommend that patients undergoing PVI should be informed of this possible complication.
Nilsson, B, et al. Increased resting heart rate following radiofrequency catheter ablation for atrial fibrillation. Europace, Vol. 7, September 2005, pp. 415-20

Editor's comment: It is always rewarding to see the findings of our LAF surveys confirmed by other studies. The following is taken from the September 2005 issue of The AFIB Report.

"Changes in heart rate after the procedures were quite common as indicated in the table below.

-	Complete Success	Partial Success	Failure	Average
Increase in heart rate	58%	59%	20%	44%
No change in rate	34%	27%	52%	40%
Decrease in rate	8%	14%	27%	16%
TOTAL	100%	100%	100%	100%

The most frequent change was an increase in heart rate (experienced by 44%). This change was most common among afibbers who had undergone successful procedure(s) (58%) and least common among those whose procedures had failed to cure the afib (20%). Statistically, the difference was very significant (p=0.0015).

The reason for the increase in heart rate after an ablation is that a significant portion of vagal nerve endings are damaged during the RF ablation procedure. Because the vagal nerves imbedded in the myocardium serve as "speed controllers" counteracting the adrenergic influence, a reduction in the number of effective vagal nerves would be expected to lead to an increased heart rate. Thus, it is possible that a more "aggressive" ablation, as indicated by a higher heart rate after the procedure, is more likely to be successful. However, this is speculation on my part and obviously assumes that the "aggression" is directed at the right spots on the atrium walls and pulmonary vein ostia.

The increase in heart rate is usually temporary and abates as the vagal nerve endings heal."

My own heart rate increased to about 95 bpm after my PVI in Bordeaux; it is now, 6 months later, down to 80 bpm and will hopefully return to my normal 60 or 65 bpm within the next 6 months. Dr. Jais suggested that increased physical activity might hasten the process towards normalcy.

COPENHAGEN, DENMARK. There is ample evidence that periodic heavy alcohol consumption (binge drinking) can trigger afib episodes. However, it is not clear whether regular alcohol consumption increases the risk of initiating AF as well. Danish researchers now report that heavy, regular alcohol consumption is indeed associated with an increased risk of initiating afib, while moderate or no alcohol consumption is not. Their study involved 7588 men (average age of 56 years) and 8827 women (average age of 57 years) enrolled in the Copenhagen City Heart Study begun in 1976. At enrolment all participants were free of coronary heart disease and previous stroke, and none used heart or antihypertensive medications.

The participants were examined in 1976-78, 1981-83, 1991-94 and at that time completed questionnaires regarding their alcohol intake. During the follow-up period (until January 1, 2001) 891 participants were hospitalized with a first episode of AF, 68 were diagnosed during one of the follow-up investigations, and 112 were both diagnosed and hospitalized. The overall incidence of new AF was 1.16% per year. This compares to an incidence rate of 1.92% observed in an older population in the USA.

The researchers found no association between moderate drinking or no drinking and the risk of initiating afib. However, men who consumed 35 or more drinks per week had a 45% greater risk of developing AF than did men who consumed less than 34 drinks a week. No excess risk was seen for women who consumed up to 21 drinks a week, which was the highest intake observed in this group. A drink was defined as one bottle of beer, one glass of wine, or one unit of spirits.

The researchers estimate that 5% of all new cases of afib among men are attributable to heavy drinking (more than 35 drinks a week). Other observed major risk factors for AF development were the development of hypertension, coronary heart disease, or congestive heart failure during follow-up. They point out that studies investigating the association between alcohol consumption and recurrent afib severity are still needed.
Mukamal, KJ, et al. Alcohol consumption and risk of atrial fibrillation in men and women. Circulation, Vol. 112, September 20, 2005, pp. 1736-42

SAN FRANCISCO, CALIFORNIA. A team of researchers from the University of California, the Massachusetts General Hospital and Boston University School of Medicine has just completed a study aimed at determining whether women with afib have a higher risk of ischemic stroke than do men. The study included 13,559 adults with atrial fibrillation. The majority of the study participants had one or more recognized risk factors for stroke, such as hypertension (57.7%), congestive heart failure (26.7%), coronary artery disease (23.9%), or diabetes (14.2%). Only 15.8% of women and 23.8% of men could be classified as non-hypertensive lone afibbers.

The overall incidence of ischemic stroke during 15,494 person years was 2.4%. The annual average rate on warfarin was 1.5% for women and 1.2% for men as compared to 3.5% and 1.8% when not on warfarin. However, the rate among lone afibbers (not on warfarin) with no additional risk factors for stroke was only 0.6% for women and 0.5% for men – in other words, no higher than would be expected in the general population.

The incidence of major hemorrhage (fatal bleeding, blood transfusion requiring two units or more of packed blood cells, or bleeding into a critical anatomical site) was 1.0% a year among warfarin-treated women and 1.1% among men. Of the major hemorrhages 0.36% among women and 0.55% among men were intracranial (hemorrhagic stroke). The authors of the study point out that, "the health consequences of intracranial hemorrhage are worse than those resulting from the ischemic strokes we seek to prevent through anticoagulation."

Fang, MC, et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation. Circulation, Vol. 112, September 20, 2005, pp. 1687-91

Editor's comment: These recent findings confirm earlier ones that neither men nor women with LONE atrial fibrillation and no other risk factors for stroke benefit from warfarin therapy. As a matter of fact, for this group the risk of major hemorrhage is almost twice as high as the risk of ischemic stroke and the risk of hemorrhagic stroke for men on warfarin is actually higher than the risk of ischemic stroke when not on warfarin. Even for lone afibbers with one additional minor risk factor such as hypertension, diabetes or age over 75 years, the benefits of warfarin therapy are not at all clear-cut. Women with one additional risk factor would have an annual ischemic stroke risk of 1.8% if not on warfarin. On warfarin this risk would be reduced to 0.7%, but would be accompanied by a 1.0% risk of major hemorrhage of which 0.36% would be associated with hemorrhagic stroke. For men the ischemic stroke risk when not on warfarin would be 1.2%. On warfarin this would be reduced to 0.7%, but would be accompanied by a 1.1% risk of major hemorrhage of which 0.55% would involve hemorrhagic stroke – in other words, pretty well a toss-up.

LEIDEN, THE NETHERLANDS. The risk of a thromboembolic event [ischemic stroke (cerebral infarction), heart attack (myocardial infarction), or peripheral arterial embolism] increases sharply with age, especially in patients with mechanical heart valve prostheses, atrial fibrillation, or a prior heart attack. These patients, especially older ones, are commonly prescribed warfarin in order to reduce the risk of a thromboembolic event. Unfortunately, warfarin therapy is associated with an increased risk of major hemorrhage (mainly gastrointestinal) and hemorrhagic stroke.

Researchers at the Leiden University Medical Center have recently completed a study to determine the relative risks of thromboembolic and bleeding events in patients treated with warfarin. The study included 4202 patients treated at a regional anticoagulation clinic. Half of these patients were on warfarin because of atrial fibrillation and their target INR was 2.5 to 3.5. The remaining patients were on warfarin because they had experienced a heart attack or had a mechanical heart valve. At baseline about 13% of patients in the entire study group was under the age of 60 years, 24% were between the ages of 60 and 70 years, 40% between 71 and 80 years, and the remaining 23% were over the age of 80 years.

Overall, the warfarin-treated patients were within their INR target range 61-68% of the time. The incidence (%/year) of ischemic stroke (fatal and non-fatal), heart attack (fatal and non-fatal), hemorrhagic stroke, and major bleeding are listed below for the various age groups.

-	Less than 60 years	61-70 years	71-80 years	80+ years
Fatal ischemic stroke	0%	0%	0%	0%
Non-fatal ischemic stroke	0.1%	0.4%	0.2%	0.5%
Fatal heart attack	0.3%	0.3%	0.3%	0.5%
Non-fatal heart attack	0.6%	0.7%	1.0%	1.3%
Total thromoembolic incidence	1.0%	1.4%	1.6%	2.4%
Fatal hemorrhagic stroke	0.1%	0.3%	0.3%	0.2%
Non-fatal hemorrhagic stroke	0%	0.2%	0.4%	0.4%
Fatal major bleeding	0%	0.04%	0.07%	0.09%
Non-fatal major bleed	0%	1.5%	1.8%	3.6%
Total bleeding incidence	1.5%	2.1%	2.5%	4.2%

From the above results it is indeed hard to conclude that warfarin therapy confers any overall benefit at any age, especially when considering only fatal strokes. It is of considerable concern that the incidence of fatal hemorrhagic strokes was about 0.3% versus 0% for ischemic stroke. A detailed breakdown is not available for atrial fibrillation patients, but the following summary data again point to a distinct disadvantage of warfarin therapy at any age.

-	Less than 60 years	61-70 years	71-80 years	80+ years
Incidence of thromboembolism	0.3%	1.6%	1.4%	1.8%
Incidence of hemorrhage	0.5%	1.9%	3.0%	4.5%

The researchers conclude that anticoagulant treatment in elderly patients presents a major clinical dilemma and state that, "The question is whether an overall benefit remains for elderly patients who are treated with oral anticoagulants."
Torn, M, et al. Risks of oral anticoagulant therapy with increasing age. Archives of Internal Medicine, Vol. 165, July 11, 2005, pp. 1527-32

Editor's comment: Although the target INR of 2.5 to 3.5 employed in this study is higher than the standard range (2.0 to 3.0) used in North America the results certainly cast considerable doubt on the benefits of warfarin therapy for stroke prevention in atrial fibrillation patients, especially those with LONE atrial fibrillation. The Dutch results also cast doubt on the generally accepted idea that afibbers over 75 years need to be on warfarin. With the incidence of hemorrhagic events being 2.5 times higher than the incidence of ischemic events for patients 80 years or older the benefits are not easy to discern.

SYRACUSE, NEW YORK. Atrial fibrillation now affects over 3 million Americans and its prevalence among people over the age of 65 years is about 6%. AF is usually associated with underlying heart disease including hypertensive heart disease, cardiomyopathy, valvular disease, or atherosclerosis. About 2-16% of all afib patients have no underlying heart abnormalities and are classified as having "lone" atrial fibrillation. In the absence of risk factors like hypertension, diabetes or previous stroke these patients have a low risk of embolism (stroke and heart attack).

Dr. Ramon Brugada of the New York Heart Center, an expert on inherited AF, estimates that up to 15% of lone afibbers may have a familial (inherited) from of the disorder. He describes his pioneering study done in 1996 of 6 Spanish families with 132 members 50 of whom were diagnosed with lone AF. The age of diagnosis varied between 0 and 45 years with 2 patients diagnosed in utero. All but two of the AF patients now have the permanent form, but in the majority of cases are asymptomatic.

Chinese researchers have also studied the genetic connection and have found two genes on chromosome II, which appear to have mutated in families with familial AF. These genes are involved in the control of potassium currents in the heart and thus the findings of the Chinese researchers confirm the role of channels responsible for potassium currents in the development of AF.

Other researchers have found a connection between genetic abnormalities in the renin-angiotensin system and the presence of non-familial AF with underlying heart disease.

Dr. Brugada concludes that efforts to control or cure AF will undoubtedly benefit from the discovery of the genes that cause the familial forms of the disease and from the knowledge of the alterations in gene expression caused by AF.
Brugada, R. Is atrial fibrillation a genetic disease? Journal of Cardiovascular Electrophysiology, Vol. 16, May 2005, pp. 553-56

ADELAIDE, AUSTRALIA. At least seven published clinical trials have concluded that infusions of magnesium sulfate are effective in reducing heart rate (ventricular response rate) in patients with supraventricular arrhythmias including atrial fibrillation.

Emergency department physicians at the Royal Adelaide Hospital have now put these findings into practice in a major evaluation. Their study included 199 patients between the ages of 60 and 80 years who were admitted with rapid AF (heart rate above 120 bpm, average of 142 bpm). The patients were randomly assigned to receive intravenous infusions of magnesium sulfate (102 patients) or placebo. The magnesium infusion consisted of 40 mEq (5 g, 20 mmol) of magnesium sulfate in 100 mL of a 5% dextrose solution. Half the solution was infused over a 20-minute period followed by the other half being infused over the following 2 hours. The placebo solution (5% dextrose) was infused in a similar manner. In addition to the magnesium infusion most patients also received a rate-reduction drug such as digoxin (79%), beta-blocker (10%), or verapamil (3%). NOTE: The reason for the predominant use of digoxin is that beta- and calcium channel blockers may cause complications in patients with poor left ventricular function. In most cases, emergency physicians do not know the underlying cardiac status of the patients, so they err on the side of caution by using digoxin, which is safe for patients with low left ventricular ejection fraction.

The authors of the study observed that 65% of the patients given magnesium sulfate experienced a reduction in heart rate to below 100 bpm, while only 34% of placebo patients did so. It was also noted that 27% of the magnesium-treated patients reverted spontaneously to sinus rhythm during the infusion, while only 12% of those in the placebo group did so.

Several adverse side effects were, however, observed during magnesium treatment. Five patients experienced hypotension (systolic blood pressure below 100 mm Hg), two experienced bradycardia, while six complained of a flushing sensation. The researchers conclude that an infusion of magnesium sulfate helps reduce heart rate and increases the likelihood of spontaneous conversion in patients with rapid afib. They caution that treating physicians should watch for hypotension and bradycardia.
Davey, MJ and Teubner, D. A randomized controlled trial of magnesium sulfate in addition to usual care, for rate control in atrial fibrillation. Annals of Emergency Medicine, Vol. 45, April 2005, pp. 347-53

Editor's comment: I am not aware of any trials where orally administered magnesium has proven successful in reducing heart rate or speeding conversion to normal sinus rhythm. It is certainly possible that it could, but the quantities to be ingested would be quite larger since 20 mEq of magnesium is equivalent to 480 mg of elemental Mg, or 6 grams of magnesium citrate. Taking this much magnesium orally over a relatively short period of time is likely to lead to a serious case of diarrhea and, due to the risk of hypotension and bradycardia, should not be attempted without medical supervision. Another approach to increasing magnesium stores fairly rapidly would be to take a hot bath with Epsom salt (magnesium sulfate), but again, I am not aware of any evidence indicating that this may be effective.

TAIPEI, TAIWAN. It is known that most afib episodes are initiated by ectopic beats originating in the pulmonary veins (PV) and that isolation of these veins can eliminate afib in 65-85% of paroxysmal afibbers. Clearly it is important to identify those patients whose main initiating areas lie outside the pulmonary veins so that an ablation can be properly directed.

Chinese researchers now report the results of an electrophysiologic study aimed at determining the prevalence and location of non-PV sources of ectopic beats. The study included 215 men and 78 women with clinically documented paroxysmal AF. The average age of the participants was 60 years and none had been able to control their afib with antiarrhythmic drugs. During the study the researchers used drugs or intermittent atrial pacing to put the patients into afib while observing where the AF-initiating ectopic beats originated. They found that the initiating beats originated in the PV in 68% of cases. In 12% of cases, the initiating beats originated in an area other than the PV, and in the remaining 20% of cases the initiating beats occurred both in and outside the PV. Of the non-PV originated episodes, 40% started out at the superior vena cava (right atrium), 34% on the left atrial posterior free wall (LAPFW), and 15% at the crista terminalis (right atrium). The researchers found that female gender was a strong predictor of initiating beats originating at the superior vena cava, while left atrial enlargement (greater than 40 mm in diameter) was a strong predictor of initiating beats originating on the back wall of the left atrium (LAPFW).

The researchers conclude that it is important to provoke ectopic beats from the superior vena cava (SVC) in women during the electrophysiologic study so that the SVC can be isolated if necessary during the ablation process. Similarly, it is important to ensure encirclement of initiating areas on the LAPFW in patients with left atrial enlargement. The patients underwent radiofrequency ablation. After a follow-up of 52 months, 67% of those with ectopic beats originating solely in the PV remained afib-free (without the use of antiarrhythmics), 76% of patients with the initiating beats located outside the PV also remained afib-free, as did 60% of those with the initiating beats originating both inside and outside the pulmonary veins.

Shih-Huang Lee, et al. Predictors of non-pulmonary vein ectopic beats initiating paroxysmal atrial fibrillation. Journal of the American College of Cardiology, Vol. 46, September 20, 2005, pp. 1054-59

Editor's comment: There is also evidence that episodes lasting longer than 24 hours may predict the presence of originating sources outside the pulmonary veins, most likely on the back wall of the left atrium.

SANTIAGO DE COMPOSTELA, SPAIN. Low-dose aspirin (acetylsalicylic acid) is widely used on a daily basis to help prevent cardiovascular events such as stroke and heart attack. Spanish researchers now report that 100 mg aspirin taken at bedtime is also effective in reducing blood pressure in patients with untreated hypertension. Their clinical trial involved 113 men and 215 women (average age of 44 years, range of 23-79 years). The participants had all been diagnosed with mild essential hypertension defined as a systolic blood pressure between 140 and 159 mm Hg or a diastolic pressure between 90 and 99 mm Hg. Heavy drinkers, smokers, and heavy exercisers were excluded from the study.

The patients were randomized into three groups and were all given appropriate diet and lifestyle instructions. The first group of 169 received no drugs, the second group of 77 patients received 100 mg aspirin upon awakening, and the third group received 100 mg aspirin before bedtime. At baseline the participants all had similar blood pressures (systolic average of 147 mm Hg, diastolic average of 85 mm Hg) and no statistically significant difference in a wide range of other variables measured. The blood pressure and heart rate of each participant were automatically measured every 20 minutes from 7 AM to 11 PM and every 30 minutes during the night for 48 hours, both at baseline and again after 3 months of the aspirin regimen.

Comparing baseline results with results after 3 months revealed no difference in blood pressure or heart rate in the control group (no aspirin). The group receiving aspirin upon awakening experienced a slight, but significant INCREASE in blood pressure during sleep (3.4 mm Hg increase in systolic and 2.0 mm Hg increase in diastolic). The group taking aspirin before bedtime, on the other hand, experienced a significant DECREASE in blood pressure, which was evident both during the day and at night (average 6.8 mm Hg drop in systolic and 4.6 mm Hg drop in diastolic). None of the groups experienced any significant differences in heart rate or a wide variety of other variables measured.

The researchers speculate that aspirin may be more effective if taken at bedtime because it inhibits both angiotensin II and renin production, which tends to peak at night. It is also possible that aspirin works by inhibiting the production of superoxide and thereby promotes the synthesis of the blood vessel wall relaxing nitric oxide. They also point out that taking aspirin in the evening rather than in the morning has been found to result in 37% fewer gastrointestinal hemorrhages. Administering aspirin at bedtime rather than in the morning has also been found beneficial in the prevention of preeclampsia, gestational hypertension, intrauterine growth retardation, and preterm delivery in high-risk pregnant women. Of course, there is also considerable evidence that daily aspirin is effective in preventing stroke and a second heart attack.
Hermida, R, et al. Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients. Journal of the American College of Cardiology, Vol. 46, September 20, 2005, pp. 975-83

Editor's comment: The finding that aspirin reduces blood pressure when taken at bedtime, but not in the morning, was reported earlier by PeggyM, one of our regular Bulletin Board contributors – it is nice to see this confirmed. The observation that aspirin "works" (for blood pressure control) when taken at bedtime, but not in the morning, is a typical example of chronobiology in action. It is to be hoped that it will give a shot in the arm to emerging field of chronopharmacology, which aims to determine the most effective time to administer common drugs. NOTE: Chinese medicine has used chronopharmacology for thousands of years. In any case, there would seem to be much to gain and nothing to lose by taking one's daily aspirin before bedtime rather than in the morning.