Abstract & Commentary
Synopsis: Intake of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), but not of aspirin, is associated with an increased risk of hypertension in women.
Source: Curhan GC, et al. Arch Intern Med. 2002;162:2204-2208.
This report comes from the Nurse’s Health Study, a prospective study of 116,671 female registered nurses enrolled in 1989. Every other year, this cohort receives questionnaires inquiring about health and lifestyle. In 1995, a subset (n = 91,744) of the entire cohort completed a longer version of the questionnaire, which collected detailed information about the use of aspirin, NSAIDs, and acetaminophen. There were 5 response categories for frequency of use (in days per month) of each of the 3 classes of analgesics: none, 1 to 4, 5 to 14, 15 to 21, and 22 or more. No data on the number of tablets a day or the dose were collected. Multiple other variables were collected and controlled for, including age, weight, smoking, family history, oral contraceptive use, and intake of alcohol sodium, potassium, and magnesium. The questionnaires queried participants about physician-diagnosed hypertension. Women who reported hypertension on any biennial questionnaire up to and including the 1995 questionnaire were excluded from analysis. Thus, women who first reported hypertension on the 1997 questionnaire were included in this analysis. Incidence of hypertension was the number of events (of new hypertension) divided by person-years of follow-up, which was broken down according to frequency of analgesic use. Relative risks (RRs) were calculated as the incidence rate of hypertension in a particular exposure (to analgesics) category divided by the corresponding rate in the comparison category. RRs were adjusted for age and potentially confounding variables.
Of the group, 51.2% used aspirin, 76.7% used NSAIDs, and 72.5% used acetaminophen at least 1 d/mo. Mean age, mean body mass index (BMI), and the proportion of women with a family history of hypertension increased with increasing frequency of analgesic use, but sodium and alcohol intake did not.
After controlling for potential confounders, intake of aspirin was not statistically associated with hypertension (although it was associated with hypertension before adjusting for other potential risk factors, including use of NSAIDs and acetaminophen).
The age-adjusted RR of hypertension was significantly increased, in a dose-dependent manner, for women who consumed NSAIDs or acetaminophen, compared with nonusers. The RR for hypertension in women taking NSAID’s or acetaminophen > 22 d/mo was 1.86 (CI, 1.51-2.28) and 2.00 (CI, 1.52-2.62) respectively.
Comment by Barbara A. Phillips, MD, MSPH
In case you are thinking that pain causes hypertension (my first thought), Curhan and colleagues point out that all 3 categories of analgesics would likely have been associated with increased blood pressure if that were the case. They also noted an increased risk of hypertension at low levels of analgesic use (1-4 d/mo), which would be an unusual pattern of treatment for chronic pain. They speculate that NSAID use might result in hypertension by causing inhibition of vasodilatory prostaglandins, sodium retention, or increased endothelin 1. They further speculate that acetaminophen use might result in hypertension by causing inhibition of cyclooxygenase, prostaglandin, or nitric oxide. In other words, it’s a mystery.
Although several other studies have examined the relationship between analgesic use and blood pressure, this is the first prospective one to look at all 3 classes of over-the-counter analgesics. Aspirin has been exonerated in 2 previous meta-analyses.1,2 There are very little data about acetaminophen use and hypertension, but NSAIDs have previously been implicated.1-3
The use of analgesics in this cohort of relatively young (aged 31-50 in 1989) women is high; more than 70% of the cohort consumed either NSAIDs or acetaminophen at least 1 d/mo. One approach that clinicians can take is to counsel those patients who are not aspirin sensitive to take aspirin, not acetaminophen or NSAIDs, for pain (and, of course, for their hearts).
Dr. Phillips, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY, is Associate Editor of Internal Medicine Alert.
References
1. Johnson AG, et al. Ann Intern Med. 1994;121:289-300.
2. Pope JE, et al. Arch Intern Med. 1993;153:477-484.
3. Gurwitz JH, et al. JAMA. 1994;272:781-786.
Although several other studies have examined the relationship between analgesic use and blood pressure, this report from the Nurses Health Study is the first prospective look at all 3 classes of over-the-counter analgesics.
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