ASPIRIN REDUCES CARDIOVASCULAR RISK IN WOMEN AND MEN

Aspirin reduces the risks of ischemic stroke in women and of myocardial infarction in men, according to the results of a meta-analysis published in the January 18 JAMA. In addition to reducing the risk of a composite of cardiovascular events, aspirin is also associated with a significantly increased risk of bleeding in both genders, the researchers found.

Jeffrey S. Berger, MD, MS, and colleagues included six randomized controlled trials for their review: Three trials included only men, two trials included both men and women, and one trial included only women. A total of 95,456 participants were enrolled in the six trials, 51,342 of whom were women. Major cardiovascular events were found in 1,285 women: 625 had strokes, 469 had myocardial infarction, and 364 experienced cardiovascular deaths. Aspirin therapy was associated with a 12% reduction in cardiovascular events and a 17% reduction in stroke, while no significant effect was observed on myocardial infarction or mortality.

Of the 44,114 men included in the six trials, 2,047 experienced major cardiovascular events. There were 597 strokes, 1,023 myocardial infarctions, and 776 cardiovascular deaths. There was a 14% reduction in cardiovascular events associated with aspirin therapy, and a 32% reduction in myocardial infarction. No significant reduction in stroke or cardiovascular mortality was observed. In both men and women, aspirin resulted in a statistically significant increased odds of major bleeding events: 301 major bleeding events occurred among women, and 288 major bleeding events occurred among men.

The researchers noted several possibilities that were suggested by previous studies as to why the specific types of benefit in cardiovascular risk differ between men and women, such as a reduced pharmacologic effect of aspirin among women compared to men, and differing event rates of stroke and myocardial infarctions between both genders. However, the researchers pointed out, "the relatively small number of [myocardial infarctions] among women and strokes among men [suggests] that further studies are needed before we can conclude that men and women differ in their cardiovascular response to aspirin."

Dr. Berger and colleagues commented, "Both the beneficial and harmful effects of aspirin should be considered by the physician and patient before initiating aspirin for the primary prevention of cardiovascular disease in both sexes."

Berger JS, Roncaglioni MC, Avanzini F, et al. Aspirin for the primary prevention of cardiovascular events in women and men. JAMA. 2006;295:306-313.

REGULAR EXERCISE MAY CUT DEMENTIA RISK AMONG SENIOR CITIZENS

Exercising at least three times a week could reduce the risk of dementia and Alzheimer’s disease among persons 65 and older, according to Eric B. Larson, MD, MPH, and colleagues. A report of their findings was published in the January 17 Annals of Internal Medicine.

At baseline, researchers assessed physical exercise habits of 1,740 persons 65 and older without cognitive impairment and asked participants the number of days per week in which they had performed various physical activities for at least 15 minutes at a time during the past year. Physical activities included walking, hiking, bicycling, aerobics, calisthenics, swimming, water aerobics, weight training or stretching, or other exercise. The participants were then followed up for a mean period of 6.2 years, with biennial examinations to identify incident dementia.

Results showed that dementia developed in 158 participants: 107 developed Alzheimer’s disease, 33 developed vascular dementia, and 18 developed other types of dementia. Of the total study cohort, 1,185 participants remained dementia-free; 121 persons withdrew from the study and the remaining 276 died. Dr. Larson and colleagues found a reduced incidence rate of dementia for persons who exercised three or more times a week compared to those who exercised fewer than three times a week; after adjustment for potential confounding factors, the reduction in risk was 32%.

In participants who had poor physical functioning at baseline, exercise was associated with the greatest reduction in risk compared to those with higher levels of physical functioning at baseline. "Low levels of physical functioning were associated with an increased risk for dementia among persons who exercised fewer than three times per week; however, this increased risk diminished among persons who exercised three or more times per week. Our finding suggests that one of the ways that exercise might reduce the risk for dementia is through modulating the relationship between physical functioning and dementia—an area worthy of additional investigation," noted the researchers.

Dr. Larson and his colleagues said the association between physical activity and a delay in onset of dementia or Alzheimer’s disease could be explained by a recent finding showing less tissue loss in the hippocampus of older persons with higher levels of physical conditioning. The researchers also pointed out that their findings did not suggest exercise prevents dementia but that exercise might be associated with a delay in dementia onset.

"Future research is needed to investigate the issue of the dose-versus-threshold–based association between exercise and onset of dementia and the relationship among physical function, exercise, and the onset of dementia," concluded the researchers.

Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81.

DEMENTIA PREDICTED MOST STRONGLY BY MIDLIFE SYSTOLIC BLOOD PRESSURE

Midlife systolic blood pressure is the strongest blood pressure component predicting incident dementia, while midlife pulse pressure and late-life blood pressure components are not independently associated with incident dementia, according to a study published in the January Stroke.

Michael H. Freitag, MD, MPH, and colleagues analyzed data of midlife blood pressure in participants of the Honolulu-Asia Aging Study from 1971 to 1974, then assessed them for late-life dementia in 1991 to 1993. Of the 3,734 men tested for dementia, 2,025 were found not to have dementia in 1991 and had complete follow-up data. This subgroup was then later reexamined for incident dementia in 1994 to 1996 and in 1997 to 1999.

Results showed that over a mean of 5.1 years of follow-up, 189 cases (7.5%) of incident Alzheimer’s disease or vascular dementia were identified. Dementia was significantly associated with systolic blood pressure, though not with pulse pressure tertiles, after adjustment for cerebrovascular risk factors. High levels of all four blood pressure components were significantly associated with dementia in patients never treated with antihypertensives. Finally, when two blood pressure components were included, only systolic blood pressure remained significant in both the total sample and in patients never treated with antihypertensives, while pulse pressure was not significantly associated with the risk of dementia.

Dr. Freitag and colleagues pointed out the previously suggested hypothesis that pulse pressure could serve both as a marker of arterial stiffness and as a precursor of hypertension. "However, it is unknown whether pulse pressure has significant direct or indirect effects on the cerebrovascular system and the brain. Secondary to brain vascular autoregulation and the distance to the aorta, it could be less affected by central pulsatile stress," they noted.

The researchers commented on several limitations to their study. Pulse pressure was measured peripherally at the brachial artery, which could lead to an underestimation of central pulse pressure, especially in elderly patients; this in turn "might be more closely related to vascular damage and disease." Second, the study was limited to elderly Japanese-American men, and "associations might be different in women, other ethnic groups or younger subjects," said Dr. Freitag and colleagues.

They concluded that the strong correlation of midlife pulse pressure and systolic blood pressure served as the main explanation between the association of midlife pulse pressure and incident dementia, while no significant information beyond systolic blood pressure alone was observed with the addition of pulse pressure to systolic blood pressure.

Freitag MH, Peila R, Masaki K, et al. Midlife pulse pressure and incidence of dementia: the Honolulu-Asia Aging Study. Stroke. 2006;37:33-37.

IBUPROFEN MAY SLOW ONSET OF PARKINSON’S DISEASE

Ibuprofen may delay or prevent the onset of Parkinson’s disease, according to Honglei Chen, MD, PhD, and colleagues. The findings were published in the December 2005 Annals of Neurology.

The researchers gathered data from the Cancer Prevention Study II Nutrition Cohort, which included 86,404 men and 97,786 women. Participants first completed a questionnaire on four types of commonly used analgesics (aspirin, acetaminophen, ibuprofen, and other nonsteroidal analgesics), then responded to four surveys, the last of which asked a question about lifetime occurrence of Parkinson’s disease. A total of 146,948 participants who completed the final questionnaire were included in the study.

Results showed that 413 incident cases of Parkinson’s disease were identified, with a significant association suggested between the cumulative updated dosage of ibuprofen and risk of Parkinson’s disease. Compared with nonusers, the relative risks were 0.73 for users of fewer than two tablets per week, 0.72 for two to 6.9 tablets per week, and 0.62 for one or more tablets per day. The association persisted after exclusion of the first two years of follow-up, exclusion of diagnoses by internists, or ending follow-up at age 75. The use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), or acetaminophen was not associated with risk of Parkinson’s disease.

Dr. Chen and colleagues commented that this study further suggests that only the use of certain nonaspirin NSAIDs, such as ibuprofen, reduces the risk of Parkinson’s disease. They stated that ibuprofen "increased the number of dopaminergic neurons in vitro and protected these neurons against glutamate neurotoxicity more so than aspirin or acetaminophen," though the researchers noted that the relevance of this observation to potential neuroprotective effects remains uncertain.

Due to scant information regarding the type and dosage of NSAIDs used by the participants, several limitations of the study included the inability to estimate the actual dose of ibuprofen, to estimate specific associations for other NSAIDs, and to create categories of use based on the biological effects of each drug.

The researchers concluded that their findings "favor the hypothesis that ibuprofen reduces the risk for development of [Parkinson’s disease]. However, there is insufficient information on the optimal dosage, and it remains uncertain whether this effect is mediated by [cyclooxygenase] inhibitions or through other mechanisms specific to ibuprofen and possibly" other NSAIDs.

Chen H, Jacobs E, Schwarzschild MA, et al. Nonsteroidal antiiflammatory drug use and the risk for Parkinson’s disease. Ann Neurol. 2005;58:963-967.

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