Do common OTC analgesics increase hypertension risk?

February 27, 2007

Boston, MA - Regular use of common analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatory drugs (NSAIDs) appears to increase the risk of hypertension, according to a new study[1]. The study, published in the February 26, 2007 issue of the Archives of Internal Medicine, was conducted by a group led by Dr John Forman (Brigham and Women's Hospital, Boston, MA).

They note that acetaminophen, ibuprofen, and aspirin are among the most commonly used drugs in the US, and two large studies (the Nurses Health Study I and II) have recently suggested these agents may be associated with an increased risk of hypertension in women, but this association has not been extensively studied in men.

Forman et al therefore studied the association between frequency of acetaminophen, NSAID, and aspirin use and the risk of incident hypertension during a four-year period among 16 031 male health professionals taking part in the ongoing prospective Health Professionals Follow-up Study. The men had an average age of 64.6 years and did not have a history of high blood pressure at baseline. The men were asked in 2000 and again in 2002 about whether and how often they used acetaminophen, NSAIDs, and aspirin. They were also asked to report if they had been diagnosed with hypertension.

Over four years of follow-up, 1968 men developed hypertension. Compared with men who did not take analgesics, those who took acetaminophen six or seven days a week had a 34% higher risk of hypertension. Those who took NSAIDs six or seven days a week had a 38% higher risk, and those who took aspirin six or seven days a week had a 26% higher risk. 

Relative risk (95% CI) of developing hypertension according to the use of analgesics (adjusted for multiple variables)

Frequency of use Once per week 2-3 times per week 4-5 times per week 6-7 times per week p for trend
Acetaminophen 1.00 (0.74-1.35) 1.00 (0.78-1.29) 1.59 (1.13-2.24) 1.34 (1.00-1.79) 0.01
NSAID 0.95 (0.77-1.18) 1.09 (0.92-1.29) 1.15 (0.85-1.54) 1.38 (1.09-1.75) 0.002
Aspirin 0.92 (0.69-1.22) 1.36 (1.14-1.61) 1.29 (1.05-1.57) 1.26 (1.14-1.40) <0.001

The researchers also looked at the total number of analgesic pills men took each week, regardless of type. Compared with men who took no pills, those who took 15 or more pills each week had a 48% higher risk of hypertension.

The authors point out that all three types of analgesic inhibit vasodilatory prostaglandins, which could explain this effect, although several other mechanisms may also be involved. "These data add further support to the hypothesis that nonnarcotic analgesics independently elevate the risk of hypertension," the authors write. "Given their common consumption and the high prevalence of hypertension, our results may have substantial public-health implications and suggest that these agents be used with greater caution," they conclude.

Messerli not convinced

But hypertension expert Dr Franz Messerli (St Luke's-Roosevelt Hospital, New York) voiced some skepticism over these results. "The study is interesting, but the odds ratios are low. In addition, these drugs are very heterogeneous, and it seems unlikely to me that they would all do the same thing in increasing the risk of hypertension when they act quite differently. Okay, prostaglandin inhibition makes some sense, but only some," he commented to heart wire .

Other considerations that Messerli says should be taken into account are that patients taking more medications will see their doctors more often and are thus more likely to have hypertension diagnosed and that chronic pain itself can increase blood pressure. Also, osteoarthritis can be associated with diabetes and metabolic syndrome, and while the authors did adjust their results for many factors, they did not correct for these two conditions, he notes.

More evidence for NSAIDs than aspirin or acetaminophen

Messerli points out that there is more evidence supporting a link with hypertension for the NSAIDs and COX-2 inhibitors, and he does believe that these drugs probably lead to an increased risk of hypertension. But he says he is not convinced of this with aspirin and acetaminophen. "I would be particularly surprised if aspirin increased blood pressure. There was an aspirin arm in the HOT hypertension study, and there was no suggestion of any such association in that trial," he said.

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