Analgesics and the Risk of Hypertension

Abstract & Commentary

By Joseph Varon, MD, FACP, FCCP, FCCM, Clinical Professor of Medicine at the University of Texas, Health Science Center, Houston; Adjunct Professor of Medicine at The University of Texas Medical Branch at Galveston. Dr. Varon reports no financial relationship to this field of study.

Synopsis: Non-narcotic analgesic use is associated with a moderate increase in hypertension in men. This association is greater with the use of non steroidal anti-inflammatory agents among obese and overweight men.

Source: Forman JP, et. al. Arch Intern Med. 2007;167:394-399.

This prospective study was aimed at evaluating the association between the use of non-narcotic analgesics and the prevalence of hypertension in the United States. The study was part of the Health Professional Follow Up Study, which is an ongoing cohort study of 51,529 male health care professionals that began in 1986. The investigators, in 2000, sought detailed information about analgesic use. Men were excluded if they died before 2000, had prevalent hypertension at baseline, were using antihypertensives or did not return the survey instrument.

The final study sample included 16,031 men and in the year 2002 a repeat survey was sent. The mean age of respondents was 64.6 years and the mean body mass index (BMI) was 24.8. A smoking history was more common with increased analgesic use.

During the study period, the investigators found a significant independent association between the frequency of analgesic use and the risk of newly diagnosed hypertension. For example, compared to non-analgesic users, men who took acetaminophen 6-7 times per week had a relative risk (RR) for hypertension of 1.34. For non-steroidal anti-inflammatory agents (NSAID) the RR was 1.38 and 1.26 for aspirin.

The study also showed that among men who took acetaminophen, the incidence of hypertension was greater in those who had a body mass index of less than 25. This was in contrast to those men who took NSAIDs, in whom the incidence of hypertension was greater in those overweight and obese and lower in those with BMI less than 25.

Commentary

This article is interesting because it provides conclusive evidence that the use of non-narcotic analgesics in men is associated with incidental hypertension. Similar results have been shown in women in the Nurse's Health Study.1

The association between acetaminophen and hypertension may be mediated through a variety of cellular mechanisms and production of mediators. For example, acetaminophen produces analgesia by inhibiting prostaglandin H2 synthetase, which is the same enzyme targeted by NSAIDs and aspirin.2 This inhibition of vasodilatory prostaglandins is partially responsible for the elevated blood pressure. Other postulated mechanisms include increases in cellular oxidative stress and reduction of endothelial function.

In other studies, analgesics have been shown to increase the risk of hypertension. In a small, randomized study of patients with known hypertension, the administration of acetaminophen given four times a day for 4 weeks vs placebo led to a 4 mm Hg increase in systolic blood pressure.3

A concern that arises when evaluating these studies is the fact that patients who take analgesics do so as the result of pain, which by itself increases the sympathetic tone and blood pressure. However, based on the study by Forman and associates,4 clinicians should be cautious about their use of non-narcotic analgesics for prolonged periods of time among their patients, as the risk of hypertension is real.

References

1. Dedier J, et. al. Hypertension. 2002;40:604-608.

2. Aronoff DM, et. al. Clin Pharmacol Ther. 2006;79:9-19.

3. Chalmers JP, et. al. Clin Exp Hypertens. 1984;6:1077-1093.

4. Forman JP, et. al. Arch Intern Med. 2007; 167: 394-399.