Analgesics, Aspirin Included, Increase Hypertension Risk

BOSTON, Feb. 26 – Daily use of over-the-counter analgesics-including aspirin-significantly increased the risk of new onset hypertension in men, researchers here reported.

These findings mirror similar findings in women reported by the same Harvard investigators last year.

Men who used acetaminophen six to seven days a week increased their risk of incident hypertension by 31% compared with non-users (P=0.05 for trend) while for other non-steroidal anti-inflammatory drugs the increase in relative risk was 33% (P=0.02 for trend).

Somewhat surprisingly, men who used aspirin for pain relief on a nearly daily basis had a 26% increase in risk for new-onset hypertension compared to non-users (P<0.001 for trend.)

Aspirin has escaped any suggestion of cardiovascular toxicity and has been generally lauded for its ability to prevent heart attacks.

For example, since early 2005 the FDA has required all NSAIDs to carry warnings about cardiovascular risks associated with prolonged, high dose use of the drugs. But aspirin was exempted from that labeling requirement because the FDA said it "has clearly been shown to reduce the risk of serious adverse cardiovascular events in certain patient populations."

The findings emerged from a study of 16,031 men enrolled in the Health Professionals Follow-up Study, said John P. Forman, M.Sc., M.D., of Brigham and Women's Hospital and Harvard Medical School. They were reported in the Feb. 26 issue of the Archives of Internal Medicine.

Dr. Forman cautioned, however, that the findings need to be carefully interpreted.

For example, patients who take aspirin to prevent heart attack should continue to take aspirin unless advised to stop doing so by their cardiologists, added coauthor Gary Curhan, M.D., Sc.D., also of Brigham and Women's Hospital and Harvard.

"However, there are many people who use these medications on a regular basis and do not realize there are potential side effects," he said. "Physicians should ask all their patients about their use of these medications and determine if there are alternatives to use."

"For example, physical therapy for those with arthritis or back pain may reduce symptoms and need for medication," he continued. "For individuals with recurrent headaches, the cause of the headaches should be explored. If the headaches can be prevented, then medication is not needed."

The prospective analysis included only men (mean age 64.6) with no history of hypertension or blood pressure-lowering medication use at baseline.

They completed a questionnaire on frequency of use and number of pills consumed per week of acetaminophen, NSAIDs, and aspirin. The questionnaire did not specify types of NSAIDs.

However, Dr. Forman said data from the cohort's female counterpart in the previous Nurses' Health Study showed "the majority of NSAIDs used were principally ibuprofen followed by naprosyn."

On a follow-up questionnaire four years later, 1,968 men reported a new diagnosis of hypertension.

Despite similar baseline blood pressure across medication use groups, the researchers found significant increases in hypertension incidence with more frequent analgesic use.

Among the findings:

•For acetaminophen, elevated risk for six to seven days per week of use (1.34, 95% CI 1.00 to 1.79, P=0.01 for trend).

•For NSAIDs, significantly elevated risk for daily or near daily use (RR 1.38, 95% CI 1.09 to 1.75 P=0.002).

•For aspirin, risk was greatest when used two or three times a week (RR 1.36, 95% CI 1.14 to 1.61) and decreased with increased use so that when taken six to seven days a week the RR was 1.26, 95% CI 1.14 to 1.40 P<0.001).

When the data were analyzed by number of pills consumed the results were similar to the findings based on frequency of use.

Conversely, body mass index (BMI) did appear to have an effect on the relationship between hypertension and analgesic use. The researchers reported:

•For acetaminophen, the risk of incident hypertension was greater among users with a BMI less than 25 whereas the association dropped out for heftier men (P=0.01 for interaction),

•For NSAIDs, risk of hypertension was greater among overweight and obese men but dropped into nonsignificance for BMI less than 25 (P=0.01 for interaction), and

•For aspirin, BMI did not appear to modify the aspirin-hypertension association (P=0.94 for interaction).

The mechanisms by which analgesics impact blood pressure may include inhibition of vasodilatory prostaglandins as well as an increase of renal tubular sodium reabsorption with NSAIDs, an increase in cellular oxidative stress with acetaminophen, and impairment of endothelial function with both acetaminophen and NSAIDs.

The researchers concluded that the "contribution of non-narcotic analgesics to the hypertension disease burden merits further study," if not more caution in their use.