From the Channing Laboratory (K.B.M., B.A.R., J.E.M., M.J.S., W.C.W.) and
Division of Preventive Medicine (J.E.M., C.H.H.), Department of Medicine,
Harvard Medical School and Brigham and Women's Hospital; and Department
of Epidemiology (K.B.M., J.E.M., M.J.S., A.M.W., W.C.W., C.H.H.),
Biostatistics (B.A.R.), and Nutrition (M.J.S., W.C.W.), Harvard School of
Public Health, Boston, Mass.
Correspondence to Dr Karin Michels, Channing Laboratory, 181 Longwood Ave, Boston, MA 02115. E-mail karin.michels{at}channing.harvard.edu
Methods and Results—A total of 14 617 women who reported
hypertension and regular use of diuretics, ß-blockers,
calcium channel blockers, ACE inhibitors, or a combination
in 1988 were included in the analyses.
Cardiovascular events and deaths were ascertained
through May 1, 1994. We documented 234 cases of myocardial infarction.
Calcium channel blocker monodrug users had an age-adjusted relative
risk (RR) of myocardial infarction of 2.36 (95% CI, 1.43 to 3.91)
compared with those prescribed thiazide diuretics. Women
prescribed calcium channel blockers had a higher prevalence of
ischemic heart disease. After adjustment for these and other
coronary risk factors, the RR was 1.64 (95% CI, 0.97 to 2.77).
Comparing the use of any calcium channel blocker (monodrug and
multidrug users) with that of any other antihypertensive agent, the
adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between
calcium channel blocker use and myocardial infarction was apparent
among women who had ever smoked cigarettes (covariate-adjusted RR,
1.81; 95% CI, 1.20 to 2.72) but not among never-smokers (RR, 0.94;
95% CI, 0.48 to 1.84).
Conclusions—In analyses adjusted only for age, we found a
significant elevation in RR of total myocardial infarction among women
who used calcium channel blockers compared with those who did not.
After adjustment for comorbidity and other covariates, the RR was
reduced. Whether the remaining observed elevated risk is real, or a
result of residual confounding by indication, or chance, or a
combination of the above cannot be evaluated with certainty on the
basis of these observational data.
In a large case-control study of hypertensives initially free of
cardiovascular disease, those who suffered an MI were
significantly more likely to have been treated with calcium channel
blockers (primarily short-acting formulations) than hypertensives who
did not suffer an MI (covariate-adjusted risk ratio, 1.62; 95% CI,
1.11 to 2.34).1 In two other case-control
studies,2 3 no increased risk was seen for
hypertensive patients on calcium channel blockers. In a recent
case-control study, 27 hypertensive patients who received short-acting
calcium channel blockers had a higher risk of
cardiovascular events than patients on the long-acting
formulation.4
In a prospective cohort study from the Established Populations for
Epidemiologic Studies of the Elderly (EPESE), among 906 hypertensives
A number of potential mechanisms for an increased risk associated with
calcium channel blockers have been proposed: proischemic,
negative inotropic, proarrhythmic, or prohemorrhagic effects, or marked
hypotension.6
The Nurses' Health Study provides the opportunity to explore the
associations between calcium channel blockers used to treat
hypertension and subsequent cardiovascular events and
mortality in a large prospective cohort of women. As was the case for
all previous populations, this cohort study was not designed a
priori to address these questions but did provide a larger number of
end points than reported previously and allowed us to assess whether
and how confounding by indication (calcium channel blockers having been
prescribed preferentially for women at higher risks) may have
influenced the results.7 8
In 1988, information was requested on the regular use of
cardiovascular medication, including thiazide
diuretics, ß-blockers, calcium channel blockers, and ACE
inhibitors. Participants were asked: "Are you currently
taking any of the following medications at least once a week?" On the
questionnaire, medications were identified only by drug class.
Information on use of calcium channel blockers was not updated until
1994; therefore, medication use was not updated in this
analysis. In 1994, 58% of women who reported use of calcium
channel blockers in 1988 still reported calcium channel blocker use.
Between 1988 and 1994, 16% of women switched from other medications to
calcium channel blockers in our study population; 15% of women
switched from diuretics to calcium channel blockers and 2%
switched from calcium channel blockers to diuretics. Overall,
the total use of calcium channel blockers in our study population
almost doubled. Because the use of long-acting calcium channel blockers
was rare in 1988, mostly short-acting formulations were likely to have
been prescribed in this population.
Hypertension, MI, angina pectoris, CABG and PTCA, stroke, and diabetes
have been assessed every 2 years since 1976. Nurses were classified as
hypertensive on the basis of self-reports of physician-diagnosed high
blood pressure. Because patients with pulmonary disease are
less likely to be prescribed ß-blockers, we assessed the prevalence
of pulmonary disorders. Pulmonary disease was defined
as asthma, chronic bronchitis, or emphysema reported through 1988. Data
on cigarette smoking (smoking status, amount of current smoking),
self-reported blood pressure and cholesterol level, height,
weight, and menopausal status were derived from the 1988
questionnaire.
The end points were first nonfatal MI or death due to coronary
disease, nonfatal or fatal stroke, total cardiovascular
events (consisting of the above plus sudden death), and total and CVD
mortality from the return of the 1988 questionnaire through May 1,
1994. Nurses who reported a nonfatal MI or stroke were asked for
permission to obtain and review their medical records. Confirmed
MIs had to meet the criteria of the World Health
Organization10 (symptoms and either typical ECG
changes or elevation of serum cardiac enzyme levels; ICDA-8 code 410).
Nonfatal strokes were confirmed if they were characterized in the
medical records as typical neurological deficits that were rapid in
onset and lasted at least 24 hours and if they met the criteria of the
National Survey of Stroke.11 According to our
review of the medical records, we classified strokes as
ischemic strokes [defined as thrombotic (with assigned ICDA-8
code 433) or embolic (ICDA-8 code 434) occlusion of a cerebral artery
or transient cerebral ischemia (ICDA-8 code 435)] or
hemorrhagic strokes [defined as subarachnoidal
hemorrhages (ICDA-8 code 430) or intraparenchymal
hemorrhages (ICDA-8 code 431)]. We excluded subdural hematomas
and strokes caused by infection or neoplasia.
Most deaths are reported by the participants' families. Mortality
surveillance includes the National Death Index to identify deaths among
nonresponders during each questionnaire cycle. Mortality follow-up is
98% complete in this cohort.12
When a death was identified, we requested written permission from the
next of kin to review medical records and obtain pathology
records. Cardiovascular mortality was defined as
death from coronary disease, stroke, or sudden death.
Coronary disease was considered the cause of death if the
medical records or autopsy report confirmed a fatal MI or if
coronary heart disease was listed as the underlying cause on
the death certificate without another more plausible cause and the
woman was known to have had coronary heart disease (ICDA 410 or
412). In no case was the cause listed on the death certificate used as
the sole criterion for death due to coronary disease. Fatal
strokes were confirmed on the basis of autopsy reports, hospital
records, or death certificates listing stroke as the underlying
cause. Sudden death was classified as death within 1 hour of symptoms
in an apparently healthy woman without evidence of coronary
heart disease or MI (ICDA-8 code 795).
All interviews and reviews of medical records were conducted by
investigators without knowledge of exposure status.
Statistical Analysis
Only first events confirmed by medical record review were counted;
therefore, women who suffered a second MI or a second stroke were
excluded from the corresponding analysis. Self-reports of
disease not confirmed by our review of the medical records (because
they were reported before baseline, the medical records did not
confirm that the women really had an MI, or we were unable to obtain
medical records) were not ignored but rather adjusted for in the
analysis. For example, 662 women reported an MI in or before
1988; of these, 259 were confirmed by medical records. The 259
women with confirmed prior MI were excluded from the analysis
of the end points MI and cardiovascular disease between
1988 and 1994. An additional 37 women were excluded from these
analyses who had reported other cardiovascular
diseases in or before 1988, but a review of their medical records
indicated that they had had an MI. Thus, our baseline population for
the analysis of MI was reduced from 14 617 to 14 321. The 403
cases of MI self-reported in or before 1988 but not confirmed were
adjusted for in the analysis. In addition, we also conducted
analyses excluding all women with self-reported prior
cardiovascular disease (nonfatal MI, stroke, CABG,
PTCA, and angina).
Person-time of follow-up was allocated to each participant starting
with the return of the 1988 questionnaire and accumulated either to May
31, 1994, the occurrence of one of the end points, or death, whichever
occurred first. Incidence or mortality rates were calculated for each
medication by dividing the number of events by the person-time of
follow-up for that agent. RRs were estimated as the ratio of incidence
rates comparing different medications. To control
simultaneously for confounding variables and risk factors
for disease, we used a pooled logistic regression model in which risk
sets were updated every 2 years.13
We used data on cardiovascular disease history in two
different ways: (1) we included in the baseline population women who
reported a diagnosis of MI or stroke that was not confirmed by our
review of the medical records or a diagnosis of CABG/PTCA or angina
pectoris and adjusted for this history in the analysis, or, in
alternative analyses, (2) we excluded all women who had
reported stroke, MI, CABG, PTCA, or angina pectoris in or before the
1988 questionnaire, thus starting with a cohort free of self-reported
cardiovascular disease in 1988. For statistical
adjustment of prior cardiovascular disease, women who
suffered more than one form of cardiovascular disease
in or before 1988 were classified according to the following hierarchy:
(1) stroke, (2) MI, (3) CABG/PTCA, (4) angina pectoris. The rationale
for the hierarchical approach is that the risk for a subset is most
likely based on the most severe condition; hence, a subject who reports
both an MI and angina pectoris has the same risk as a woman with an MI
alone.
Of the 14 617 women included in this analysis, 385 suffered a
first fatal or nonfatal cardiovascular event between
1988 and 1994 (234 MIs, 162 strokes, and 12 sudden deaths, not mutually
exclusive) (Tables 3A
We also compared the risk of a first MI for hypertensive women who
reported regular calcium channel blocker use (as monotherapy or
combination therapy) with that for hypertensive women who received
other antihypertensive medication(s) (Table 3A
When only women who were free of cardiovascular disease
(stroke, MI, CABG, PTCA, angina pectoris) in 1988 were considered, age-
and covariate-adjusted RRs differed considerably less (Table 3B
To account for possible effects of duration of use of calcium channel
blockers as well as misclassification due to discontinuation of the
drug, we considered women who answered both the 1988 and the 1994
questionnaires. Women who reported calcium channel blocker use in 1988
and 1994 had an RR of nonfatal MI of 1.82 (95% CI, 1.03 to 3.23)
compared with those on other antihypertensive agents. Women who
reported use in 1988 but not in 1994 had an RR of nonfatal MI of 2.72
(95% CI, 1.57 to 4.70), and those who reported use in 1994 but not in
1988 had an RR of 2.57 (1.78 to 3.74) compared with women on other
antihypertensive agents.
Results for smoking-specific subgroups are presented in Table 5
Overall, 551 women died during the follow-up period (Table 6
There was no evidence of effect modification by diabetes in our
population (data not shown).
In observational epidemiological studies, it is difficult to determine
whether drugs that are considered more "potent" may be given to
patients at higher risk for the outcome being evaluated. Such
confounding by indication would make the more effective drugs appear
more harmful simply because patients for whom they are prescribed were
at higher risk because of other baseline risk factors or prior disease.
It is generally difficult to exclude all such bias in an observational
study as severity of disease may be difficult to assess with sufficient
precision.
After women with prior stroke, MI, CABG, PTCA, or angina were excluded
from our analyses, age-adjusted and covariate-adjusted RRs for
calcium channel blocker users differed only marginally. The remaining
elevation in risk could reflect a real effect, residual confounding by
indication, the play of chance, or any combination of the above. For
residual confounding by indication by prior disease to explain the
remaining elevated RR, a considerable proportion of nurses who did not
report cardiovascular disease or
cardiovascular risk factors by 1988 would actually have
to have had those, and such underlying unreported
cardiovascular disease would have to be differential
with respect to calcium channel blocker use. To explain the observed RR
of 1.6 for MI, about half the nurses on calcium channel blockers would
have had to be so misclassified.
Although the sample size is large, this prospective cohort study was
not designed specifically to test the hypotheses addressed. We had to
rely on self-reported medication use; however, because the study
population consists of health professionals, the reliability of such
data can be assumed to be high. Doses and duration of use were not
known. Furthermore, because the use of calcium channel blockers was
assessed only in 1988 and 1994, new and preexisting prescriptions could
not be separated, so we could not determine with certainty the
indications for which the various drugs were prescribed. Because the
total use of calcium-channel blockers in our study population almost
doubled in that interval, and many more women switched from
diuretics to calcium channel blockers than vice versa, the use
of baseline classification of drug use as exposure may underestimate
the association between calcium antagonists and disease
incidence rather than overestimate it. The RR for nonfatal MI was not
stronger among women who remained on calcium channel blockers between
1988 and 1994, however, than for women who reported use only in 1988 or
in 1994. Although we also have no information on short-acting versus
long-acting formulations of calcium channel blockers, in 1988 most
formulations were almost certainly short-acting, as opposed to the
situation today.
In subgroup data, a significantly elevated risk of MI among women who
reported regular use of calcium channel blockers was apparent among
ever- (current or former) but not among never-smokers. These findings
could well be due to chance, but are also compatible with a possible
pharmacological interaction between calcium channel blockers and
smoking. It may also be the case that all the residual confounding is
concentrated in the higher-risk group, the smokers. No important
modification by smoking was observed for total mortality. In a prior
large case-control study, there was no significant difference in the
risk ratio of MI associated with the use of calcium channel blockers
for current smokers (1.86) and nonsmokers (1.53); however, former
smokers were combined with nonsmokers in the
analysis.1 Further investigations of the
role of smoking with respect to the use of calcium channel blockers are
needed.
Differential effects of antihypertensive drugs in smokers and
nonsmokers have been reported previously. In the MRC trial of treatment
of mild hypertension, the event rates for stroke and for all
cardiovascular events among patients on
propranolol were reduced only among nonsmokers but not
among smokers (P=.03 and P=.01,
respectively).14
Pharmacological treatment of mild to moderate hypertension with
diuretics and ß-blockers has been shown to reduce stroke, MI,
and vascular mortality.15 16 17 Although calcium
channel blockers and ACE inhibitors have clear
antihypertensive effects, almost two decades after their introduction
their risk-to-benefit ratio has not been tested directly in
large-scale, randomized trials. Nonetheless, because of their
apparently lower side effects and some pharmacological benefits, the
number of prescriptions for calcium channel blockers and ACE
inhibitors for the treatment of hypertension has risen
rapidly during the past decade.18 19 20 21 Our study
population reflected these changes in prescription pattern; women who
reported new onset of hypertension in 1988 reported a relatively larger
percentage of ACE inhibitor and calcium
antagonist use than of diuretics and ß-blockers
(data not shown).
In 1988, the Joint National Committee on the Detection, Evaluation, and
Treatment of High Blood Pressure recommendations listed calcium channel
blockers and ACE inhibitors as first-line choices, besides
diuretics and ß-blockers (JNC-IV).22
Lack of data on morbidity and mortality for calcium channel blockers
and ACE inhibitors led national committees such as the JNC
in 1993 (JNC-V)23 as well as the World Health
Organization and the International Society of
Hypertension24 in 1997 to recommend initial
monotherapy with diuretics and/or ß-blockers for
hypertension, and reserved calcium channel blockers and ACE
inhibitors as second-line choices when diuretics
and ß-blockers have proved unacceptable or ineffective. The National
Heart, Lung, and Blood Institute recently stated that "...
short-acting nifedipine should be used with great caution
(if at all), especially at higher doses, in the treatment of
hypertension, angina, and MI."25 Recently, the
JNC-VI recommendations have reaffirmed diuretics and
ß-blockers as first-line choices and reserved calcium channel
blockers for special indications.26
In general, data on drug efficacy and safety from observational studies
have to be interpreted with considerable caution, because residual
confounding by indication may remain even after careful consideration
of other risk factors and comorbidity. In these circumstances, for
small to moderate effects, randomized trials specifically designed to
compare efficacies and adverse effects of the various antihypertensive
medications are advantageous. The recent Syst-Eur trial indicated net
cardiovascular benefit of the medium-acting calcium
channel blocker nitrendipine compared with placebo among patients with
isolated systolic hypertension.27 Because
no comparison with other antihypertensives was made, inferences on the
relative efficacy of calcium channel blockers cannot be made from this
trial.
Because short-acting calcium channel blockers have largely been
supplanted by long-acting formulations in clinical practice today,
clinical trials that are currently under way are randomizing
long-acting calcium channel blockers against other antihypertensive
agents, including the first-line drugs, diuretics and
ß-blockers. Whether short-acting calcium channel blockers have
harmful effects compared with other antihypertensive agents may never
be completely resolved.
Received August 11, 1997;
revision received December 18, 1997;
accepted December 19, 1997.
2.
Jick H, Derby LE, Gurewich V, Vasilakis C. The risk of
myocardial infarction associated with antihypertensive drug treatment
in persons with uncomplicated essential hypertension.
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Aursnes I, Litleskare I, Frøyland H, Abdelnoor M.
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© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Prospective Study of Calcium Channel Blocker Use, Cardiovascular Disease, and Total Mortality Among Hypertensive Women
The Nurses' Health Study
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—In several observational studies, patients
prescribed calcium channel blockers had higher risks of
cardiovascular diseases and mortality than those
prescribed other antihypertensive medications. We explored these
associations in the Nurses' Health Study.
Key Words: calcium channels • cardiovascular diseases • mortality • epidemiology
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
In
some but not all observational studies, both case-control and cohort,
patients prescribed calcium channel blockers for hypertension had
higher risks of cardiovascular diseases and mortality
than those prescribed other antihypertensive medications. 
71 years old, there were 30 deaths among those who self-reported use
of (mainly short-acting) nifedipine compared with 91 among
those who used ß-blockers, yielding an RR of 1.7 (95% CI, 1.1 to
2.7).5 There was no apparent association for
other calcium channel blockers (verapamil or diltiazem) or
for ACE inhibitors relative to ß-blockers.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Study Population and Data Collection
The Nurses' Health Study cohort was established in 1976, when
121 701 female registered US nurses 30 to 55 years old returned
completed questionnaires sent by mail. Participants are followed
through biennial self-administered questionnaires. On baseline and
follow-up questionnaires, nurses have been asked to provide demographic
and lifestyle information as well as their disease
status.9
Analyses were restricted to women who reported
physician-diagnosed hypertension in 1988 or on any previous
questionnaire and who reported in 1988 that they regularly took
diuretics, ß-blockers, calcium channel blockers, or ACE
inhibitors or any combination. Women who reported use of
both calcium channel blockers and ACE inhibitors were
excluded because of a sample size (n=196) that was too small to provide
us with reliable estimates. Women were also excluded from the
analysis if their covariate information was incomplete (n=91),
leaving a study population of 14 617 women. During the 6-year
observation period, 551 women (3.8%) died and 400 (2.7%) were lost to
follow-up.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
The distribution of risk factors among women prescribed
antihypertensive medications is given in Table 1
. Women who reported the use of calcium
channel blockers also reported somewhat higher cholesterol
levels, diabetes, and pulmonary disease. Calcium channel
blockers were preferentially prescribed for higher-risk hypertensive
patients diagnosed with ischemic heart disease (MI or angina
pectoris) (Table 2).
View this table:
[in a new window]
Table 1. Risk Factor Profile and Regular Use of Thiazide
Diuretics (TD), ß-Blockers (BB), Calcium Channel Blockers
(CCB), ACE Inhibitors (ACE), and Their Combinations
Self-Reported in 1988 Among 14 617 Participants of the Nurses' Health
Study Who Had Reported Hypertension in 1988 or Before (Column
Percentages in Parentheses)
View this table:
[in a new window]
Table 2. Profile of Self-Reported Diseases Before or in 1988
and Use of TD, BB, CCB, ACE Inhibitors, and Their
Combinations Self-Reported in 1988 Among 14 617 Participants of the
Nurses' Health Study Who Had Reported Hypertension in 1988 or Before and 4). The age-adjusted risk of a first MI was
increased among women who reported use of calcium channel blockers
alone (RR, 2.36; 95% CI, 1.43 to 3.91) or in combination with
diuretics or ß-blockers (RR, 3.43; 95% CI, 2.23 to 5.27)
relative to women on thiazide diuretics alone (Table 3A). Adjustment for a history of stroke,
CABG/PTCA, angina, diabetes, pulmonary disease, and numerous
other risk factors for cardiovascular disease reduced
the association considerably, but it remained elevated (calcium channel
blocker monotherapy: RR, 1.64; 95% CI, 0.97 to 2.77; combination
therapy: RR, 1.88; 95% CI, 1.18 to 3.01). A similar observation was
made for total cardiovascular events, although
associations were less strong (Table 3A). RRs for
stroke were not significantly different for users of calcium channel
blockers from those for users of other medications, but numbers of
events were smaller (Table 4).
View this table:
[in a new window]
Table 3A. RR (95% CI) of Total (Fatal and Nonfatal) MI and
Cardiovascular Disease (CVD) Between 1988 and 1994
According to Medication Status Self-Reported in 1988 Among Women of the
Nurses' Health Study Who Had Reported Hypertension in 1988 or
Before
View this table:
[in a new window]
Table 3B. RR (95% CI) of Total (Fatal and Nonfatal) MI and
Cardiovascular Disease (CVD) Between 1988 and 1994
According to Medication Status Self-Reported in 1988 Among Women of the
Nurses' Health Study Who Had Reported Hypertension in 1988 or Before
and Were Free of CVD (Stroke, MI, CABG/PTCA, Angina Pectoris) in 1988
View this table:
[in a new window]
Table 4. RR (95% CI) of Total (Fatal and Nonfatal) Stroke,
Hemorrhagic (Fatal and Nonfatal) Stroke, and Ischemic (Fatal
and Nonfatal) Stroke Between 1988 and 1994 According to Medication
Status Self-Reported in 1988 Among 14 468 Women1
of the Nurses'
Health Study Who Had Reported Hypertension in 1988 or Before 
). RRs adjusted only for
age (2.10; 95% CI, 1.53 to 2.89) decreased to 1.42 (95% CI, 1.01 to
2.01) after adjustment for prior disease and pertinent covariates. ). The
age-adjusted RR for MI among calcium channel blocker monodrug users
compared with women on diuretics was 1.82 (95% CI, 0.89 to
3.70), and the covariate-adjusted value was 1.65 (95% CI, 0.81 to
3.38); the corresponding estimates among multidrug users were 2.48
(95% CI, 1.26 to 4.90) and 2.29 (95% CI, 1.15 to 4.54). . When only women who ever smoked were
considered, the disease- and covariate-adjusted RR of MI was 1.81 (95%
CI, 1.20 to 2.72), compared with 0.94 (95% CI, 0.48 to 1.84) among
never-smokers (Table 5) (test for statistical interaction:
2P=.12). Because we could not determine smoking status at
the start of calcium channel blocker prescription and we were
interested in a possible pharmacological interaction between medication
use and smoking, we present data for current and former smokers
combined (ie, ever-smokers). Women who smoked in 1988, however, had a
covariate-adjusted association between calcium channel blocker use and
MI similar to that of women who were former smokers in 1988 (current
smokers in 1988: RR, 1.83; 95% CI, 0.97 to 3.46; former smokers in
1988: RR, 1.92; 95% CI, 1.12 to 3.28). Among women free of
self-reported cardiovascular disease in 1988, the
difference in the association of risk with calcium channel blocker use
between ever-smokers and never-smokers was even stronger and
statistically significant: ever-smokers who reported the use of calcium
channel blockers had a covariate-adjusted RR for MI of 2.23 (95% CI,
1.28 to 3.89), whereas the estimate among never-smokers was 0.65 (95%
CI, 0.20 to 2.12) (test for statistical interaction:
2P=.045).
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[in a new window]
Table 5. RR (95% CI) of Total MI, Total
Cardiovascular (CVD) Events, and Total Strokes Between
1988 and 1994 Comparing Women Who Reported Use of Calcium Channel
Blockers (CCB) (Monodrug and Multidrug Users) With Women Who Reported
Use of Other Antihypertensives in 1988 Stratified by Smoking Status ). Total mortality was higher for women
who reported use of calcium channel blockers than for women on
diuretics (monodrug users: RR, 1.64; 95% CI, 1.17 to 2.29),
but this estimate was reduced in magnitude after adjustment for
potential confounders (RR, 1.30; 95% CI, 0.91 to 1.85) (Table 6). The
elevated RR was partly due to a somewhat higher
cardiovascular mortality among women reporting calcium
channel blocker use. Noncardiovascular mortality was
also somewhat elevated for calcium antagonist users, which
was largely due to deaths other than cancer. The covariate-adjusted RRs
for total mortality for calcium channel blocker users (monodrug and
multidrug users) was 1.44 (95% CI, 1.14 to 1.82) overall, 1.37 (95%
CI, 1.03 to 1.83) among women who had ever smoked, and 1.54 (95% CI,
1.01 to 2.35) among never-smokers compared to women on other
antihypertensive medication.
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[in a new window]
Table 6. RR (95% CI) of Total (All-Cause) Mortality,
Cardiovascular (CVD) Mortality, and Mortality From
Other Causes Between 1988 and 1994 According to Medication Status
Self-Reported in 1988 Among 14 617 Women of the Nurses' Health Study
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
In this prospective cohort study, a greater proportion of women
prescribed calcium channel blockers had risk factors for
cardiovascular disease and prior diseases, specifically
ischemic heart disease, pulmonary disease, and
diabetes. Our primary analysis included women with
cardiovascular comorbidity, because this is
representative of the patient population actually
treated with antihypertensive agents in clinical practice. In
analyses adjusted only for age, we observed significant
elevations in RRs for total MI and cardiovascular
events as well as cardiovascular and total mortality
among women prescribed calcium channel blockers. Statistical adjustment
for comorbidity and other prevalent risk factors reduced the RRs for
all endpoints.
Selected Abbreviations and Acronyms
CABG
=
coronary artery bypass graft
JNC
=
Joint National Committee
MI
=
myocardial infarction
PTCA
=
percutaneous transluminal coronary angioplasty
RR
=
relative risk
Acknowledgments
This work was supported by research grants HL-34594 and CA-40356
from the National Institutes of Health, Bethesda, Md. The authors thank
Professor Frank E. Speizer, MD, principal investigator of the Nurses'
Health Study, for his leadership and for helpful advice on the
analysis and on the manuscript. We also thank the participants
of the Nurses' Health Study for providing the relevant information
necessary for this analysis.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
Psaty BM, Heckbert SR, Koepsell TD, Siscovick DS,
Raghunathan TE, Weiss NS, Rosendaal FR, Lemaitre RN, Smith NL, Wahl PW,
Wagner EH, Furberg CD. The risk of myocardial infarction associated
with antihypertensive drug therapies. JAMA. 1995;274:620–625.
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