 |
|
Frequency of Analgesic Use and Risk of Hypertension in Younger Women
Gary C. Curhan, MD, ScD;
Walter C. Willett, MD, DrPH;
Bernard Rosner, PhD;
Meir J. Stampfer, MD, DrPH
Arch Intern Med. 2002;162:2204-2208.
ABSTRACT
| |
Background In addition to their antipyretic, anti-inflammatory, and pain-relieving
effects, analgesics may interfere with blood pressure regulation. However,
little prospective information is available on the association between analgesic
use and the risk of hypertension.
Methods We performed a prospective study of 80 020 women aged 31 to 50
years who participated in the Nurses' Health Study II and had no previous
history of hypertension. Frequency of use (in days per month) of aspirin,
nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen was collected
by mailed questionnaire in 1995. Incident cases of physician-diagnosed hypertension
were identified by self-report on the 1997 biennial questionnaire.
Results During 164 090 person-years of follow-up, 1650 incident cases of
hypertension were identified. At least 1 d/mo, 51.2% of the cohort used aspirin,
76.7% used NSAIDs, and 72.5% used acetaminophen. After adjusting for age,
all 3 classes of analgesics were associated with an increased risk of incident
hypertension (P<.001 for trend). After further
adjustment for all 3 analgesics and other potential risk factors, only NSAIDs
and acetaminophen (P<.001 for trend for both)
were significantly associated with risk of hypertension. Compared with nonusers,
the relative risk of hypertension for women taking NSAIDs 22 d/mo or more
was 1.86 (95% confidence interval, 1.51-2.28) and for those taking acetaminophen
22 d/mo or more was 2.00 (95% confidence interval, 1.52-2.62).
Conclusions Use of NSAIDs and use of acetaminophen were significantly associated
with increased risk of hypertension, but aspirin use was not. A substantial
proportion of hypertension in the United States, and the associated morbidity
and mortality, may be due to the use of these medications.
INTRODUCTION
ANALGESIC USE is common, particularly in women.1 In
1999, more than $2 billion was spent on over-the-counter analgesic medications
in the United States alone (Roland Schneider, MD, Boehringer-Ingelheim, e-mail,
August 24, 2000). The antipyretic, anti-inflammatory, and pain-relieving actions
of analgesics are well-known. Analgesics may interfere with blood pressure
regulation by altering production of vasodilatory prostaglandins,2 decreasing renal sodium excretion,3 or
inhibiting nitric oxide synthetase.4-5
Results of previous studies have suggested that use of nonsteroidal
anti-inflammatory drugs (NSAIDs) causes a small increase in blood pressure6 and increases the risk of hypertension,7 whereas
aspirin6, 8 and acetaminophen9 use do not. However, most studies have focused on
changes in blood pressure in individuals taking antihypertensive medication.
Despite the high prevalence of use of analgesics, often for prolonged periods,
scant information is available on the long-term risk of incident hypertension.
To address this issue, we prospectively examined the association between
frequency of use of the 3 analgesic classes and risk of incident hypertension
among 80 020 young women with no previous history of hypertension.
METHODS
STUDY POPULATION
In 1989, 116 671 female registered nurses (age range, 25-42 years)
from 15 states completed and returned the initial questionnaire and constitute
the Nurses' Health Study II cohort. This cohort is followed by means of biennial
mailed questionnaires that inquire about lifestyle practices, other exposures
of interest, and the incidence of physician-diagnosed disease. The follow-up
rate for the cohort exceeds 90%.
Detailed information on analgesic use was first collected on the 1995
biennial questionnaire. For this study of analgesic use and the risk of hypertension
between 1995 and 1997, participants were selected based on having responded
to the longer version of the 1995 biennial questionnaire (n = 91 744).
After excluding women with a previously reported history of hypertension (n
= 8999) and those who did not answer the 1997 follow-up questionnaire (n =
2725), 80 020 women were included in the analysis.
ASSESSMENT OF ANALGESIC USE
We first asked about the frequency of use of each of the 3 classes of
analgesics—aspirin, NSAIDs, and acetaminophen—on the 1995 biennial
questionnaire. There were 5 response categories of frequency of use (in days
per month) for each of the 3 classes of analgesics: none, 1 to 4, 5 to 14,
15 to 21, and 22 or more. Information on number of tablets per day or dose
was not collected.
ASSESSMENT OF OTHER EXPOSURES
On the 1995 questionnaire, we obtained updated information on age, weight,
smoking, and oral contraceptive use. From the 1995 food-frequency portion
of the questionnaire, we assessed the intake of alcohol, sodium, potassium,
and magnesium. Information available from the 1989 baseline Nurses' Health
Study II questionnaire included height, systolic blood pressure (9 response
categories), diastolic blood pressure (7 response categories), and family
history of hypertension. On the 1991 questionnaire, we inquired about a variety
of physical activities from which we calculated a metabolic equivalent task
score. Body mass index (BMI) was calculated as weight in kilograms divided
by the square of height in meters. On the 1995 questionnaire, we obtained
information on the following health screening behaviors in the previous 2
years: sigmoidoscopy or colonoscopy, mammography, breast examination by a
clinician, bimanual pelvic examination, and ovarian ultrasound. We obtained
information on the 1997 questionnaire on the following health screening behaviors
in the previous 2 years: sigmoidoscopy or colonoscopy, mammography, and bimanual
pelvic examination.
ASSESSMENT OF HYPERTENSION
The baseline and follow-up biennial questionnaires inquired about physician-diagnosed
hypertension and the year of diagnosis. Self-reported diagnosis of hypertension
was found to be reliable in a similar cohort of women, the Nurses' Health
Study I.10 A study participant was considered
to have a history of hypertension if she reported high blood pressure on any
questionnaire up to and including the 1995 questionnaire; these women were
excluded from the analysis. We included as cases only individuals who first
reported hypertension on the 1997 questionnaire and whose date of diagnosis
was after the return of the 1995 questionnaire.
STATISTICAL ANALYSIS
For each participant, person-months of follow-up were counted from the
date of the return of the 1995 questionnaire to the date of return of the
1997 questionnaire. We allocated person-months of follow-up according to exposure
status in 1995 (as indicated by the category of frequency of analgesic use
and other variables) and calculated incidence as the number of events divided
by person-years of follow-up.
The relative risk (RR)—the incidence rate among women in a particular
category of exposure divided by the corresponding rate in the comparison category—was
used as the measure of association.11 Age-adjusted
RRs were calculated after stratification according to 5-year age categories.11 The Mantel extension test was used to evaluate linear
trends across categories of analgesic use.12 In
addition, RRs were adjusted simultaneously for potentially confounding variables
using multiple logistic regression analysis. The variables considered in the
primary multivariate models were age (5-year categories), BMI (6 categories),
alcohol intake (6 categories), sodium intake (quintiles), family history of
hypertension in 1989 (yes or no), oral contraceptive use in 1995 (yes or no),
and frequency of use of the individual analgesics (5 categories for each analgesic).
Categories for missing values for individual variables were also included.
In separate models, we also adjusted for age in 1-year increments and BMI
in deciles. We also examined models that were further adjusted for current
smoker (yes or no), physical activity in 1991 (metabolic equivalent task scores
in quintiles), quintiles of intake of potassium and magnesium, and systolic
(8 categories) and diastolic (6 categories) blood pressure in 1989. Multivariate
tests for trend for the analgesics were assessed using the midpoint of the
frequency category. For all RRs, we calculated 95% confidence intervals (CIs).
All P values are 2-tailed. This study was approved
by the Partners HealthCare institutional review board, Boston, Mass.
RESULTS
During 164 090 person-years of follow-up, 1650 incident cases of
hypertension were identified. Overall, 51.2% of the cohort used aspirin at
least 1 d/mo, 76.7% used NSAIDs, and 72.5% used acetaminophen. Among women
taking an analgesic 22 d/mo or more, NSAIDs were the most commonly used analgesic
class, being taken by 4.9% of the cohort.
Characteristics of the cohort according to frequency of use category
of the individual analgesics are given in Table 1. Mean age increased with increasing frequency of use of
aspirin and NSAIDs. Mean BMI increased with increasing frequency of use of
all 3 analgesics. Intake of alcohol and sodium and mean systolic and diastolic
blood pressures did not differ substantially by frequency of analgesic use.
Oral contraceptive use was least common among women who consumed any of the
analgesics 22 d/mo or more. The proportion of women with a family history
of hypertension increased with increasing frequency of analgesic use.
|
|
|
|
Table 1. Characteristics of the Cohort According to Frequency of Analgesic
Use in 1995 in the Nurses' Health Study II*
|
|
|
Information on frequency of use was unavailable from 27% of the cohort
for aspirin, 8% of the cohort for NSAIDs, and 14% of the cohort for acetaminophen.
It is unclear why these questions were unanswered by some participants. Overall,
the characteristics listed in Table 1 were
similar in participants who did and did not answer the specific analgesic
questions.
ASPIRIN
Compared with nonusers of aspirin, the age-adjusted RR of hypertension
was significantly increased in women who consumed aspirin, even for those
using aspirin 1 to 4 d/mo (RR, 1.18; 95% CI, 1.02-1.35) (Table 2), and the trend was highly statistically significant (P<.001). After adjusting for the use of NSAIDs and acetaminophen
and for other potential risk factors, the RRs were attenuated and the trend
was only marginally statistically significant (P =
.07) (Table 2).
|
|
|
|
Table 2. Age-Adjusted and Multivariate Relative Risks (RRs) for Incident
Hypertension According to Category of Analgesic Use*
|
|
|
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
Compared with nonusers of NSAIDs, the age-adjusted RR of hypertension
was significantly increased for women who consumed NSAIDs, even for women
who used NSAIDs 1 to 4 d/mo (RR, 1.17; 95% CI, 1.02-1.36) (Table 2). There seemed to be a dose response between frequency of
use of NSAIDs and risk of hypertension, and the trend was highly statistically
significant (P<.001). After adjusting for use
of the other 2 analgesics and other risk factors, the RRs for the individual
categories were attenuated but remained statistically significant, as did
the trend (P<.001 for trend) (Table 2). Compared with nonusers, the RR of hypertension for women
taking NSAIDs 22 d/mo or more was 1.86 (95% CI, 1.51-2.28).
ACETAMINOPHEN
Compared with nonusers of acetaminophen, the age-adjusted RR of hypertension
was significantly increased, even for women using acetaminophen 1 to 4 d/mo
(RR, 1.22; 95% CI, 1.07-1.39) (Table 2).
There seemed to be a dose response between frequency of acetaminophen use
and risk of hypertension, and the trend was highly statistically significant
(P<.001). After adjusting for other risk factors,
the RRs for the individual categories were attenuated but remained statistically
significant, as did the trend (P<.001 for trend).
Compared with nonusers, the RR of hypertension for women taking acetaminophen
22 d/mo or more was 2.00 (95% CI, 1.52-2.62).
Controlling for age in 1-year increments and BMI in deciles or further
adjustment for current smoking, physical activity in 1991, intake of potassium
and magnesium in 1995, and systolic and diastolic blood pressure in 1989 did
not materially change the results. When the analyses were limited to women
who had a screening examination in 1995 and 1997 (n = 65 648), the results
were not substantially altered. After limiting the analyses to women who had
complete information on frequency of use of all 3 analgesics (n = 53 904),
the results for the age-adjusted and multivariate models were essentially
unchanged.
EFFECT MODIFICATION
We explored whether the associations between the different analgesics
and risk of incident hypertension were modified by age, BMI, or family history
of hypertension. Only family history seemed to modify the associations. The
magnitudes of the RRs for all 3 analgesics were generally higher in participants
without a family history than in those with a family history. The tests for
interaction were marginally statistically significant (aspirin, P = .06; NSAIDs, P = .10; and acetaminophen, P = .09).
COMMENT
The use of NSAIDs and the use of acetaminophen were each strongly associated
with risk of developing hypertension in women, and the risks increased with
increasing frequency of use. The use of aspirin did not seem to be associated
with risk.
To our knowledge, this is the first prospective study to examine frequency
of use of the 3 classes of nonnarcotic analgesics, which are readily available
without a prescription, in relation to risk of hypertension. The frequency
of use of all 3 classes of analgesics is high. More than 70% of the cohort
consumed either NSAIDs or acetaminophen at least 1 d/mo. Thus, if these associations
are shown to be causal, their contribution to the number of individuals who
develop hypertension is likely to be substantial.
The lack of an association between aspirin use and risk of hypertension
is consistent with previous studies. Two meta-analyses6, 8 found
no change in blood pressure in short-term studies of aspirin use. A prospective
study13 of Swiss factory workers found that
women who had aspirin detected in their urine at baseline were more likely
to develop hypertension during follow-up (P = .11),
but there was no information on frequency of use or adjustment for other potential
risk factors.
Our finding that the use of NSAIDs was associated with an increased
risk of hypertension is supported by previous studies. In the meta-analysis
by Johnson et al,6 use of NSAIDs was associated
with an increase in blood pressure of 5.0 mm Hg (95% CI, 1.2-8.7 mm Hg). This
effect was most marked in hypertensive individuals who were taking antihypertensive
medication.6 A meta-analysis by Pope and colleagues8 found that the effect of NSAID use on blood pressure
varied considerably. Notably, 92% of individuals in that meta-analysis were
hypertensive. In a case-control study, Gurwitz et al7 found
that among individuals 65 years and older, the odds ratio for the initiation
of antihypertensive therapy for recent users of NSAIDs was 1.66 compared with
nonusers. The interpretation of previously published studies is limited by
several factors. The prospective studies usually lasted no more than a few
weeks. Sample sizes tended to be small, and little information was available
on younger women. Finally, the studies rarely focused on individuals without
a history of hypertension.
Use of NSAIDs may raise blood pressure through inhibition of production
of vasodilatory prostaglandins,2 sodium retention,3 or possibly increased endothelin 1 production.14 Because of its ready availability over the counter,
ibuprofen is the most commonly used NSAID in this cohort (G.C.C., unpublished
data, 1999). Our findings indicate that use of NSAIDs increases the risk of
hypertension, even when taken infrequently. We did not detect significant
interactions for NSAIDs with age, BMI, or family history of hypertension.
Little information is available in the literature regarding the effect
of acetaminophen use on blood pressure. Short-term studies9, 15 have
found no effect of acetaminophen use on blood pressure in treated hypertensive
individuals. We did not find any case-control or prospective studies of the
association between acetaminophen use and hypertension. Acetaminophen is a
weak inhibitor of peripheral cyclooxygenase, but it may be a potent inhibitor
of prostaglandin production in the central nervous system.16 In
addition, acetaminophen use may inhibit nitric oxide production,5 which
could lead to increased vascular tone and blood pressure. However, the mechanism
for the increased risk of hypertension we observed is unknown.
Acute pain can lead to an increase in blood pressure by increasing sympathetic
activity. However, scant information is available on the impact of chronic
pain on blood pressure. Although chronic pain in frequent analgesic users
could be a possible explanation for our findings, we would have expected an
increased risk for all 3 analgesics; however, no association was observed
for aspirin. It is possible that the underlying condition(s) (eg, rheumatoid
arthritis) for which the participants took the analgesics is associated with
an increased risk of hypertension, but we believe that this is unlikely. After
we adjusted for self-reported rheumatoid arthritis, the RRs did not change.
In addition, the increase in risk for NSAIDs and acetaminophen was significant
at levels of use as low as 1 to 4 d/mo. This low frequency of use would be
an unusual pattern for treatment of chronic pain. Finally, we would have expected
similar risks for all 3 classes of analgesics.
Several limitations of this study should be addressed. This study was
limited to women aged 31 to 50 years. We did not directly measure the participants'
blood pressure, and the diagnosis of hypertension was self-reported. We do
not have information on which women had blood pressure measured during follow-up.
It is possible that women who were taking analgesics more frequently were
more likely to visit a physician and have their blood pressure checked. However,
we would have expected that this would have led to detection bias for any
of the analgesics, yet no independent association was observed for aspirin
use. In addition, when we limited the analysis to women who had at least 1
type of screening examination in 1995 and 1997, the results were essentially
unchanged. The proportion of participants with missing information on frequency
of use ranged from 7.9% for NSAIDs to 27.4% for aspirin. The characteristics
listed in Table 1 did not differ
substantially between those with and without missing information; however,
it is possible that there were unrecognized factors that may be associated
with frequency of analgesic use and with hypertension. Finally, as we do not
have information on duration of analgesic use, it is unclear how long the
medications need to be used before the risk begins to increase.
In conclusion, these findings indicate that use of NSAIDs and use of
acetaminophen are associated with increased risk of hypertension but that
aspirin use is not. A substantial proportion of hypertension in the United
States, and the associated morbidity and mortality, may potentially be due
to the use of NSAIDs and acetaminophen. Given that these medications are readily
available over the counter and are used by a large proportion of the adult
population, this association merits additional study.
AUTHOR INFORMATION
Accepted for publication April 3, 2002.
This work was supported by grants DK52866, CA87969, and CA50385 from
the National Institutes of Health, Bethesda, Md.
We thank the participants in the Nurses' Health Study and the Nurses'
Health Study II and Sharon Curhan, MD, Elaine Coughlan, BS, Kris Vernon, Karen
Corsano, BA, Gary Chase, BA, Julie Herbstman, BA, and Jennifer Atkinson, BA,
for their contributions to this project.
Corresponding author and reprints: Gary C. Curhan, MD, ScD, Channing
Laboratory, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA 02115
(e-mail: Gary.Curhan{at}channing.harvard.edu).
From the Channing Laboratory, Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School (Drs Curhan, Willett, Rosner, and Stampfer),
and the Departments of Nutrition (Drs Willett and Stampfer) and Epidemiology
(Drs Curhan and Stampfer), Harvard School of Public Health, Boston, Mass.
REFERENCES
| |
1. Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population
of the United States: the Slone survey. JAMA. 2002;287:337-344.
FREE FULL TEXT
2. Bjorkman DJ. The effect of aspirin and nonsteroidal anti-inflammatory drugs on prostaglandins. Am J Med. 1998;105(suppl 2):8S-12S.
3. Patrono C, Dunn MJ. The clinical significance of inhibition of renal prostaglandin synthesis. Kidney Int. 1987;32:1-12.
ISI
| PUBMED
4. Amin AR, Attur MG, Pillinger M, Abramson SB. The pleiotropic functions of aspirin: mechanisms of action. Cell Mol Life Sci. 1999;56:305-312.
FULL TEXT
|
ISI
| PUBMED
5. Ryu YS, Lee JH, Seok JH, et al. Acetaminophen inhibits iNOS gene expression in RAW 264.7 macrophages:
differential regulation of NF-  by acetaminophen and salicylates. Biochem Biophys Res Commun. 2000;272:758-764.
FULL TEXT
|
ISI
| PUBMED
6. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? a meta-analysis
[see Comments]. Ann Intern Med. 1994;121:289-300.
FREE FULL TEXT
7. Gurwitz JH, Avorn J, Bohn RL, Glynn RJ, Monane M, Mogun H. Initiation of antihypertensive treatment during nonsteroidal anti-inflammatory
drug therapy. JAMA. 1994;272:781-786.
ABSTRACT
8. Pope JE, Anderson JJ, Felson DT. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs
on blood pressure. Arch Intern Med. 1993;153:477-484.
ABSTRACT
9. Radack KL, Deck CC, Bloomfield SS. Ibuprofen interferes with the efficacy of antihypertensive drugs: a
randomized, double-blind, placebo-controlled trial of ibuprofen compared with
acetaminophen. Ann Intern Med. 1987;107:628-635.
10. Colditz GA, Martin P, Stampfer MJ, et al. Validation of questionnaire information on risk factors and disease
outcomes in a prospective cohort study of women. Am J Epidemiol. 1986;123:894-900.
FREE FULL TEXT
11. Rothman KJ. Modern Epidemiology. Boston, Mass: Little Brown & Co Inc; 1986.
12. Mantel N. Chi-square tests with one degree of freedom: extensions of the Mantel-Haenszel
procedure. J Am Stat Assoc. 1963;58:690-700.
FULL TEXT
|
ISI
13. Dubach UC, Rosner B, Sturmer T. An epidemiologic study of abuse of analgesic drugs: effects of phenacetin
and salicylate on mortality and cardiovascular morbidity (1968 to 1987) [see
Comments]. N Engl J Med. 1991;324:155-160.
ABSTRACT
14. Johnson AG, Nguyen TV, Owe-Young R, Williamson DJ, Day RO. Potential mechanisms by which nonsteroidal anti-inflammatory drugs
elevate blood pressure: the role of endothelin-1. J Hum Hypertens. 1996;10:257-261.
ISI
| PUBMED
15. Chalmers JP, West MJ, Wing LM, Bune AJ, Graham JR. Effects of indomethacin, sulindac, naproxen, aspirin, and paracetamol
in treated hypertensive patients. Clin Exp Hypertens A. 1984;6:1077-1093.
ISI
| PUBMED
16. Clissold SP. Paracetamol and phenacetin. Drugs. 1986;32:46-59.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Hypertension in rheumatoid arthritis
Panoulas et al.
Rheumatology (Oxford) 2008;47:1286-1298.
ABSTRACT
| FULL TEXT
Does paracetamol cause hypertension?
Montgomery
BMJ 2008;336:1190-1191.
FULL TEXT
Treatment of Persistent Shoulder Pain with Sodium Hyaluronate: A Randomized, Controlled Trial. A Multicenter Study
Blaine et al.
JBJS 2008;90:970-979.
ABSTRACT
| FULL TEXT
A Risk Score for Predicting Near-Term Incidence of Hypertension: The Framingham Heart Study
Parikh et al.
ANN INTERN MED 2008;148:102-110.
ABSTRACT
| FULL TEXT
Renal function and cognition in the 1932 Scottish Mental Survey Lothian cohort
Munang et al.
Age Ageing 2007;36:323-325.
FULL TEXT
Frequency of Analgesic Use and Risk of Hypertension Among Men
Forman et al.
Arch Intern Med 2007;167:394-399.
ABSTRACT
| FULL TEXT
Nonsteroidal Antiinflammatory Drugs, Acetaminophen, and the Risk of Cardiovascular Events
Chan et al.
Circulation 2006;113:1578-1587.
ABSTRACT
| FULL TEXT
Habitual Caffeine Intake and the Risk of Hypertension in Women
Winkelmayer et al.
JAMA 2005;294:2330-2335.
ABSTRACT
| FULL TEXT
Analgesic Use and Risk of Subsequent Hypertension in Apparently Healthy Men
Kurth et al.
Arch Intern Med 2005;165:1903-1909.
ABSTRACT
| FULL TEXT
Non-Narcotic Analgesic Dose and Risk of Incident Hypertension in US Women
Forman et al.
Hypertension 2005;46:500-507.
ABSTRACT
| FULL TEXT
Long-term Use of Aspirin and Nonsteroidal Anti-inflammatory Drugs and Risk of Colorectal Cancer
Chan et al.
JAMA 2005;294:914-923.
ABSTRACT
| FULL TEXT
Folate Intake and the Risk of Incident Hypertension Among US Women
Forman et al.
JAMA 2005;293:320-329.
ABSTRACT
| FULL TEXT
Hypertension and Cyclooxygenase-2 Inhibitors: Target: The Renal Medulla
Hao and Breyer
Hypertension 2004;44:396-397.
FULL TEXT
Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic
WARNER and MITCHELL
FASEB J. 2004;18:790-804.
ABSTRACT
| FULL TEXT
Acute Congestive Heart Failure Induced by Rofecoxib
Campbell and Sneed
J Am Board Fam Med 2004;17:131-135.
FULL TEXT
Both Thrombotic and Nonthrombotic Cardiovascular and Cerebrovascular Side Effects of Nonsteroidal Anti-Inflammatory Drugs Should Be Considered
Stollberger and Finsterer
Stroke 2004;35
:e26-e26.
FULL TEXT
Effects of Acetaminophen on Myocardial Infarct Size in Rats
Dai and Kloner
J CARDIOVASC PHARMACOL THER 2003;8:277-284.
ABSTRACT
Analgesics and Hypertension: Causality or Correlation?
Glaser
Arch Intern Med 2003;163:1114-1114.
FULL TEXT
NSAIDs and Hypertension
Aisen et al.
Arch Intern Med 2003;163:1115-1115.
FULL TEXT
Acetaminophen and Hypertension: A Causal Association or Pain Mediated?
Brotman
Arch Intern Med 2003;163:1113-1114.
FULL TEXT
Hypertension and Obesity
Najman et al.
Arch Intern Med 2003;163:1114-1115.
FULL TEXT
Analgesic Use and Risk for Hypertension in Younger Women
JWatch Women's Health 2002;2002:3-3.
FULL TEXT
In brief
BMJ 2002;325:986-986.
FULL TEXT
|
