Stefan N. Willich

Concurrent Morning Increase in Platelet Aggregability and the Risk of Myocardial Infarction and Sudden Cardiac Death

Abstract We have previously reported that the frequencies of myocardial infarction and of sudden cardiac death are highest during the period from 6 a.m. to noon. Since platelet aggregation may have a role in triggering these disorders, we measured platelet activity at 3-hour intervals for 24 hours in 15 healthy men. In vitro platelet responsiveness to either adenosine diphosphate (ADP) or epinephrine was lower at 6 a.m. (before the subjects arose) than at 9 a.m. (60 minutes after they arose). The lowest concentration of these agents required to produce biphasic platelet aggregation decreased (i.e., aggregability increased) from a mean ±SEM of 4.7±0.6 to 3.7±0.6 μM (P<0.01) for ADP and from 3.7±0.8 to 1.8±0.5 μM (P<0.01) for epinephrine. The period from 6 to 9 a.m. was the only interval in the 24-hour period during which platelet aggregability increased significantly. We subsequently studied 10 subjects on alternate mornings after they arose at the normal time and after delayed arising. The morning increas...

Circadian variation in the frequency of sudden cardiac death.

To determine whether sudden cardiac death exhibits a circadian rhythm similar to that recently demonstrated for nonfatal myocardial infarction, we analyzed the time of day of sudden cardiac death as indicated by death certificates of 2203 individuals dying out of the hospital in Massachusetts in 1983. The data reveal a prominent circadian variation of sudden cardiac death, with a low incidence during the night and an increased incidence from 7 to 11 A.M. The pattern is remarkably similar to that reported for nonfatal myocardial infarction and episodes of myocardial ischemia. The finding that the frequency of sudden cardiac death is increased in the morning is compatible with hypotheses that sudden cardiac death results from ischemia or from a primary arrhythmic event. Further study of the physiologic changes occurring in the morning may provide new information supporting or refuting these hypotheses, thereby leading to increased understanding and possible prevention of sudden cardiac death.

Physical Exertion as a Trigger of Acute Myocardial Infarction

BACKGROUND It is controversial whether the onset of myocardial infarction occurs randomly or is precipitated by identifiable stimuli. Previous studies have suggested a higher risk of cardiac events in association with exertion. METHODS Consecutive patients with acute myocardial infarction were identified by recording all admissions to our hospital in Berlin and by monitoring a general population of 330,000 residents in Augsburg, Germany. Information on the circumstances of each infarction was obtained by means of standardized interviews. The data analysis included a comparison of patients with matched controls and a case-crossover comparison (one in which each patient serves as his or her own control) of the patients usual frequency of exertion with the last episode of exertion before the onset of myocardial infarction. RESULTS From January 1989 through December 1991, 1194 patients (74 percent of whom were men; mean age [+/- SD], 61 +/- 9 years) completed the interview 13 +/- 6 days after infarction. We found that 7.1 percent of the case patients had engaged in physical exertion (> or = 6 metabolic equivalents) at the onset of infarction, as compared with 3.9 percent of the controls at the onset of the control event. For the patients as compared with the matched controls, the adjusted relative risk of having engaged in strenuous physical activity at the onset of infarction or the control event was 2.1 (95 percent confidence interval, 1.1 to 3.6). The case-crossover comparison yielded a similar relative risk of 2.1 (95 percent confidence interval, 1.6 to 3.1) for having engaged in strenuous physical activity within one hour before myocardial infarction. Patients whose frequency of regular exercise was less than four and four or more times per week had relative risks of 6.9 and 1.3, respectively (P < 0.01). CONCLUSIONS A period of strenuous physical activity is associated with a temporary increase in the risk of having a myocardial infarction, particularly among patients who exercise infrequently. These findings should aid in the identification of the triggering mechanisms for myocardial infarction and improve prevention of this common and serious disorder.

Exercise and Acute Cardiovascular Events: Placing the Risks Into Perspective: A Scientific Statement From the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology

Habitual physical activity reduces coronary heart disease events, but vigorous activity can also acutely and transiently increase the risk of sudden cardiac death and acute myocardial infarction in susceptible persons. This scientific statement discusses the potential cardiovascular complications of exercise, their pathological substrate, and their incidence and suggests strategies to reduce these complications. Exercise-associated acute cardiac events generally occur in individuals with structural cardiac disease. Hereditary or congenital cardiovascular abnormalities are predominantly responsible for cardiac events among young individuals, whereas atherosclerotic disease is primarily responsible for these events in adults. The absolute rate of exercise-related sudden cardiac death varies with the prevalence of disease in the study population. The incidence of both acute myocardial infarction and sudden death is greatest in the habitually least physically active individuals. No strategies have been adequately studied to evaluate their ability to reduce exercise-related acute cardiovascular events. Maintaining physical fitness through regular physical activity may help to reduce events because a disproportionate number of events occur in least physically active subjects performing unaccustomed physical activity. Other strategies, such as screening patients before participation in exercise, excluding high-risk patients from certain activities, promptly evaluating possible prodromal symptoms, training fitness personnel for emergencies, and encouraging patients to avoid high-risk activities, appear prudent but have not been systematically evaluated.

Circadian variation in the incidence of sudden cardiac death in the framingham heart study population

To determine if sudden cardiac death shows circadian variation, the time of day of sudden cardiac deaths in the Framingham Heart Study was analyzed. Analysis was based on mortality data collected in a standardized manner for the past 38 years for each death among the 5,209 persons in the original cohort. The necessary assumptions about the cause and timing of unwitnessed deaths were made in a manner likely to diminish the possibility of detecting an increased incidence of sudden cardiac death during the morning. In the Framingham study, analyses using these assumptions reveal a significant circadian variation (p less than 0.01) in occurrence of sudden cardiac death (n = 429), with a peak incidence from 7 to 9 AM and a decreased incidence from 9 AM to 1 PM. Risk of sudden cardiac death was at least 70% higher during the peak period than was the average risk during other times of the day. Further studies are needed to confirm this finding in other populations, to collect data regarding medications and to determine activity immediately before sudden cardiac death. Investigation of physiologic changes occurring during the period of increased incidence of sudden cardiac death may provide increased insight into its causes and suggest possible means of prevention.

Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis:

Background Over the past several decades, numerous large cohort studies have attempted to quantify the protective effect of physical activity on cardiovascular and all-cause mortality. The aim of the authors’ review was to provide an up-to-date overview of the study results. Methods In a systematic MEDLINE search conducted in May 2007, the authors included cohort studies that assessed the primary preventive impact of physical activity on all-cause and cardiovascular mortality. The authors reported risk reductions on the basis of comparison between the least active and the most active population subgroups, with the least active population subgroup as the reference group. Random-effect models were used for meta-analysis. Results A total of 33 studies with 883372 participants were included. Follow-up ranged from 4 years to over 20 years. The majority of studies reported significant risk reductions for physically active participants. Concerning cardiovascular mortality, physical activity was associated with a risk reduction of 35% (95% confidence interval, 30–40%). All-cause mortality was reduced by 33% (95% confidence interval, 28–37%). Studies that used patient questionnaires to assess physical activity reported lower risk reductions than studies that used more objective measures of fitness. Conclusions Physical activity is associated with a marked decrease in cardiovascular and all-cause mortality in both men and women, even after adjusting for other relevant risk factors.

Obesity prevalence from a European perspective: a systematic review

BackgroundObesity has been recognised as an important contributing factor in the development of various diseases, but comparative data on this condition are limited. We therefore aimed to identify and discuss current epidemiological data on the prevalence of obesity in European countries.MethodsWe identified relevant published studies by means of a MEDLINE search (1990–2008) supplemented by information obtained from regulatory agencies. We only included surveys that used direct measures of weight and height and were representative of each countrys overall population.ResultsIn Europe, the prevalence of obesity (body mass index ≥ 30 kg/m2) in men ranged from 4.0% to 28.3% and in women from 6.2% to 36.5%. We observed considerable geographic variation, with prevalence rates in Central, Eastern, and Southern Europe being higher than those in Western and Northern Europe.ConclusionIn Europe, obesity has reached epidemic proportions. The data presented in our review emphasise the need for effective therapeutic and preventive strategies.

Acupuncture in patients with osteoarthritis of the knee: a randomised trial.

BACKGROUND Acupuncture is widely used by patients with chronic pain although there is little evidence of its effectiveness. We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with osteoarthritis of the knee. METHODS Patients with chronic osteoarthritis of the knee (Kellgren grade < or =2) were randomly assigned to acupuncture (n=150), minimal acupuncture (superficial needling at non-acupuncture points; n=76), or a waiting list control (n=74). Specialised physicians, in 28 outpatient centres, administered acupuncture and minimal acupuncture in 12 sessions over 8 weeks. Patients completed standard questionnaires at baseline and after 8 weeks, 26 weeks, and 52 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index at the end of week 8 (adjusted for baseline score). All main analyses were by intention to treat. RESULTS 294 patients were enrolled from March 6, 2002, to January 17, 2003; eight patients were lost to follow-up after randomisation, but were included in the final analysis. The mean baseline-adjusted WOMAC index at week 8 was 26.9 (SE 1.4) in the acupuncture group, 35.8 (1.9) in the minimal acupuncture group, and 49.6 (2.0) in the waiting list group (treatment difference acupuncture vs minimal acupuncture -8.8, [95% CI -13.5 to -4.2], p=0.0002; acupuncture vs waiting list -22.7 [-27.5 to -17.9], p<0.0001). After 52 weeks the difference between the acupuncture and minimal acupuncture groups was no longer significant (p=0.08). INTERPRETATION After 8 weeks of treatment, pain and joint function are improved more with acupuncture than with minimal acupuncture or no acupuncture in patients with osteoarthritis of the knee. However, this benefit decreases over time.

Effects of gender and race on prognosis after myocardial infarction: Adverse prognosis for women, particularly black women

Controversy has arisen concerning whether gender influences the prognosis after myocardial infarction. Although some studies have shown there to be no difference between the sexes, most have indicated a worse prognosis for women, attributing this to differences in baseline characteristics. It has been further suggested that black women have a particularly poor prognosis after infarction. To determine the contribution of gender and race to the course of infarction, 816 patients with confirmed myocardial infarction who were enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) were analyzed. Of those patients, 226 were women and 590 were men, 142 were black and 674 were white. The cumulative mortality rate at 48 months was 36% for women versus 21% for men (p less than 0.001, mean follow-up 32 months). The cumulative mortality rate by race was 34% for blacks versus 24% for whites (p less than 0.005). Both women and blacks exhibited more baseline characteristics predictive of mortality than did their male or white counterparts. It was possible to account for the greater mortality rate of blacks by identifiable baseline variables; however, even after adjustment, the mortality rate for women remained significantly higher (p less than 0.002). The poorer prognosis for women was influenced by a particularly high mortality rate among black women (48%); the mortality rate for white women was 32%, for black men 23% and for white men 21%. The mortality for black women was significantly greater than that of the other subgroups. Thus, findings in the MILIS population indicate that the prognosis after myocardial infarction is worse for women, particularly black women.

The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain

Abstract In a pooled analysis of four randomized controlled trials of acupuncture in patients with migraine, tension‐type headache, chronic low back pain, and osteoarthritis of the knee we investigated the influence of expectations on clinical outcome. The 864 patients included in the analysis received either 12 sessions of acupuncture or minimal (i.e. sham) acupuncture (superficial needling of non‐acupuncture points) over an 8 week period. Patients were asked at baseline whether they considered acupuncture to be an effective therapy in general and what they personally expected from the treatment. After three acupuncture sessions patients were asked how confident they were that they would benefit from the treatment strategy they were receiving. Patients were classified as responders if the respective main outcome measure improved by at least fifty percent. Both univariate and multivariate analyses adjusted for potential confounders (such as condition, intervention group, age, sex, duration of complaints, etc.) consistently showed a significant influence of attitudes and expectations on outcome. After completion of treatment, the odds ratio for response between patients considering acupuncture an effective or highly effective therapy and patients who were more sceptical was 1.67 (95% confidence interval 1.20–2.32). For personal expectations and confidence after the third session, odds ratios were 2.03 (1.26–3.26) and 2.35 (1.68–3.30), respectively. Results from the 6‐month follow‐up were similar. In conclusion, in our trials a significant association was shown between better improvement and higher outcome expectations.