Volume 2, Number 4: April
1999
Passive Smoking and the Risk of Coronary Heart Disease -- A Meta-Analysis of Epidemiologic Studies
Passive Smoking and
the Risk of Coronary Heart Disease -- A Meta-Analysis of
Epidemiologic Studies
Source: N Engl J Med 1999;340:920-6
Background. The effect of passive smoking on the risk of coronary
heart disease is controversial. We conducted a meta-analysis of
the risk of coronary heart disease associated with passive
smoking among nonsmokers.
Methods. We searched the Medline and Dissertation Abstracts
Online data bases and reviewed citations in relevant articles to
identify 18 epidemiologic (10 cohort and 8 case-control) studies
that met prestated inclusion criteria. Information on the designs
of the studies, the characteristics of the study subjects,
exposure and outcome measures, control for potential confounding
factors, and risk estimates was abstracted independently by three
investigators using a standardized protocol.
Results. Overall, nonsmokers exposed to environmental smoke had a
relative risk of coronary heart disease of 1.25 (95 percent
confidence interval, 1.17 to 1.32) as compared with nonsmokers
not exposed to smoke. Passive smoking was consistently associated
with an increased relative risk of coronary heart disease in
cohort studies (relative risk, 1.21; 95 percent confidence
interval, 1.14 to 1.30), in case-control studies (relative risk,
1.51; 95 percent confidence interval, 1.26 to 1.81), in men
(relative risk, 1.22; 95 percent confidence interval, 1.10 to
1.35), in women (relative risk, 1.24; 95 percent confidence
interval, 1.15 to 1.34), and in those exposed to smoking at home
(relative risk, 1.17; 95 percent confidence interval, 1.11 to
1.24) or in the workplace (relative risk, 1.11; 95 percent
confidence interval, 1.00 to 1.23). A significant dose-response
relation was identified, with respective relative risks of 1.23
and 1.31 for nonsmokers who were exposed to the smoke of 1 to 19
cigarettes per day and those who were exposed to the smoke of 20
or more cigarettes per day, as compared with nonsmokers not
exposed to smoke (P=0.006 for linear trend).
Conclusions. Passive smoking is associated with a small increase
in the risk of coronary heart disease. Given the high prevalence
of cigarette smoking, the public health consequences of passive
smoking with regard to coronary heart disease may be important.
Exertional
Leg Symptoms Other Than Intermittent Claudication Are Common in
Peripheral Arterial Disease
Source: Arch Intern Med. 1999;159:387-392
Background: Epidemiological data show that most
community-dwelling men and women with lower-extremity peripheral
arterial disease (PAD) do not have typical symptoms of
intermittent claudication. We compared the prevalence of
intermittent claudication, leg symptoms other than intermittent
claudication, and absence of exertional leg symptoms between
patients with PAD identified from a blood flow laboratory (group
1), patients with PAD in a general medicine practice (group 2),
and control patients without PAD (group 3).
Methods: Numbers of participants in groups 1, 2, and 3 were 137,
26, and 105, respectively. Patients with previously diagnosed PAD
were excluded from groups 2 and 3. All participants underwent
ankle-brachial index measurement and were administered the San
Diego claudication questionnaire to assess leg symptoms.
Results: Within groups 1, 2, and 3, prevalences of intermittent
claudication were 28.5% (n=39), 3.8% (n=1), and 3.8% (n=4),
respectively. Prevalences of exertional leg symptoms other than
intermittent claudication were 56.2% (n=77), 42.3% (n=11), and
19.0% (n=20), respectively. Absence of exertional leg symptoms
was reported by 15.3% (n=21), 53.8% (n=14), and 77.1% (n=81),
respectively. Among
patients with PAD, older age, male sex, diabetes mellitus, and
group 2 vs group 1 status were associated independently with
absence of exertional leg symptoms in multivariable regression
analysis. Lower ankle-brachial index levels and group 1 vs group
2 status were associated with intermittent claudication.
Conclusions: Clinical manifestations of PAD are diverse,
particularly among patients identified by ankle-brachial index
screening. Exertional leg symptoms other than intermittent
claudication are common in PAD. Patients with PAD who are older,
male, diabetic, or identified with ankle-brachial index screening
in a primary care setting are more likely to have asymptomatic
PAD.
COMMENT
Intermittent claudication is considered the most classic
manifestation of PAD and is described as the "earliest
manifestation" or "most common symptom" in PAD.
However, among white women participating in the Study of
Osteoporotic Fractures, only 18% of women found to have PAD by
ABI screening had intermittent claudication. Similarly, in the
Cardiovascular Health Study, 12% of men and women aged 65 years
and older had an abnormally low ABI, while just 2% had
intermittent claudication symptoms.
It is unclear from studies of community-dwelling men and women,
such as those in the Study of Osteoporotic Fractures and the
Cardiovascular Health Study, whether people with low ABI who do
not have intermittent claudication are asymptomatic or have leg
symptoms other than classic intermittent claudication. The
generalizability of findings from community-based studies to
patients encountered by practicing clinicians is also unclear.
Among participants with PAD in the Cardiovascular Health Study
and the Study of Osteoporotic Fractures, 40% and 45%,
respectively, had an ABI of 0.80 or greater and less than 0.90,
indicative of mild disease. In contrast, 14% of patients with PAD
in the present study had an ABI of 0.80 or greater and less than
0.90. Thus, most patients with PAD described herein had more
severe disease than the previously described men and women with
PAD in epidemiological studies.
The most striking implication of our data is that the clinical
manifestations of PAD are diverse among patients with ABI less
than 0.90 at an academic medical center. Identifying the full
spectrum of PAD requires attention to symptoms other than classic
intermittent claudication and possibly screening for PAD even
among asymptomatic patients. In the present study, 29% of
patients with PAD identified
from the blood flow laboratory had classic intermittent
claudication, compared with 4% of patients with PAD identified
with ABI screening in a general internal medicine practice and 4%
of normal controls. Thus, the sensitivity of intermittent
claudication for PAD appears higher in a blood flow laboratory
setting than among patients with PAD identified with ABI
screening from a general medicine practice. This discrepancy is
in part caused by selection bias, since all patients with PAD
recruited from the blood flow laboratory were referred by a
physician who suspected PAD, whereas patients identified from
general internal medicine had previously unrecognized disease.
The PAD may have been unrecognized among
general medicine patients in part because 96% did not have
typical intermittent claudication symptoms.
The high prevalence of pain at rest among patients with PAD in a
general medicine practice was unexpected and should be
distinguished from PAD-related rest pain, a symptom of severe
ischemic disease that typically increases when the affected leg
is elevated. In our study, pain at rest was defined as any
exertional leg pain that also occurs at rest. Since none of the
patients with PAD from general medicine had previously diagnosed
disease, it is highly unlikely that these patients were
experiencing severe ischemia. Perhaps patients with PAD recruited
from general medicine were experiencing mild arterial ischemia at
rest. Alternatively, they may have confused other types of pain
occurring at rest with their exertional leg symptoms.
While comorbid diseases may contribute to the high prevalence of
exertional leg symptoms other than intermittent claudication in
PAD, at least 2 factors make this unlikely. Aside from diabetic
neuropathy, we know of no biologically plausible explanation for
a higher prevalence of comorbidities causing exertional leg
symptoms, such as spinal stenosis or lower-extremity arthritis,
among patients with PAD as compared with patients without PAD.
Although diabetic neuropathy might increase the prevalence of
atypical exertional leg symptoms or pain at rest, our logistic
regression analysis showed that diabetes mellitus was associated
independently with asymptomatic PAD. Therefore, our comparisons
of leg
symptoms between PAD and control patients should represent valid
differences in leg symptoms caused by the presence or absence of
PAD.
Our data suggest that among patients with PAD, older age,
diabetes mellitus, male sex, and ABI screening in a general
medicine practice are associated with absence of exertional leg
symptoms. The association between asymptomatic PAD and older age
may in part be caused by lower activity levels among the elderly,
since greater physical activity levels may be necessary to induce
exertional leg symptoms. Similarly, increasing exercise duration
may be more likely to precipitate lower-extremity arterial
ischemia, accounting for the positive relationship observed
between exercise duration and intermittent claudication. Our data
suggest that screening for PAD with the ABI may be especially
useful among older, diabetic, male patients in a general medicine
setting. Physical examination is neither sensitive nor specific
for diagnosing PAD in community-based or hospital settings.
We are aware of only 1 other report describing the spectrum of
leg symptoms among patients with PAD in a patient care
setting.Criqui et al described leg symptoms in a blood flow
laboratory population including 88% men and 4% African Americans.
Criqui et al reported a 26% prevalence of intermittent
claudication and a 25% prevalence of pain at rest. Although their
results are generally consistent with ours, the 31% prevalence of
asymptomatic PAD reported by Criqui et al is twice that reported
herein for patients from a blood flow laboratory. Our data add to
the work of Criqui et al by assessing the prevalence of leg
symptoms among patients with PAD in a general medical setting and
control
patients without PAD.
Our study had a few limitations. Our data reflect patients at 1
medical center, and results may not be generalizable to patients
with PAD at other institutions. Exclusion of non-English-speaking
patients may limit the generalizability of our findings to
patients who do not speak English. However, the consistency of
our findings for patients with PAD from a blood flow laboratory
with those reported by Criqui et al
suggests that our data are similar to those of other academic
medical centers. Second, many potentially eligible subjects could
not be reached, refused participation, or had transportation
difficulties, limiting study enrollment. Severity of PAD was
comparable between potentially eligible patients with PAD and
participating patients with PAD from the blood flow laboratory.
Potentially eligible patients with PAD who refused participation
were slightly older than participants with PAD from the blood
flow laboratory. Because increasing age was associated with a
lower prevalence of exertional leg symptoms, it is conceivable
that our results underestimate the prevalence of asymptomatic PAD
among patients at a blood flow laboratory. Finally, the absolute
number of patients with PAD identified with ABI screening in
general medicine was small. Further study is necessary to confirm
our findings for patients with PAD identified with ABI screening
from primary care physicians' practices.
The 13% prevalence of previously undiagnosed PAD among men and
women in our general medicine practice suggests that PAD may
regularly go unrecognized in primary care settings, perhaps
because the high prevalence of asymptomatic disease and
exertional leg symptoms other than intermittent claudication are
underappreciated by clinicians. Recognizing PAD, even when
asymptomatic, is important because PAD has significant
implications for cardiovascular morbidity and mortality. Our data
highlight the need for a better understanding of the spectrum of
clinical pictures presented by a broad range of patients with
PAD.
Prevention of a
First Stroke : A Review of Guidelines and a Multidisciplinary
Consensus
Statement From the National Stroke Association
Source: JAMA. 1999;281:1112-1120
Objective To establish, in a single resource, up-to-date
recommendations for primary care physicians regarding prevention
strategies for a first stroke.
Participants Members of the National Stroke Association's (NSA's)
Stroke Prevention Advisory Board and Cedars-Sinai Health System
Department of Health Services Research convened on April 9, 1998,
in an open meeting. The conference attendees, selected to
participate by the NSA, were recognized experts in neurology (9),
cardiology (2), family practice (1), nursing (1), physician
assistant practices (1),
and health services research (2).
Evidence A literature review was carried out by the Department of
Health Services Research, Cedars-Sinai Health System, Los
Angeles, Calif, using the MEDLINE database search for 1990
through April 1998 and updated in November 1998. English-language
guidelines, statements, meta-analyses, and overviews on
prevention of a first stroke were reviewed.
Consensus Process At the meeting, members of the advisory board
identified 6 important stroke risk factors (hypertension,
myocardial infarction [MI], atrial fibrillation, diabetes
mellitus, blood lipids, asymptomatic carotid artery stenosis),
and 4 lifestyle factors (cigarette smoking, alcohol use, physical
activity, diet).
Conclusions Several interventions that modify well-documented and
treatable cardiovascular and cerebrovascular risk factors can
reduce the risk of a first stroke. Good evidence for direct
stroke reduction exists for hypertension treatment; using
warfarin for patients after MI who have atrial fibrillation,
decreased left ventricular ejection fraction, or left ventricular
thrombus; using 3-hydroxy-3 methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors for patients after MI;
using warfarin for patients with atrial fibrillation and specific
risk factors; and performing carotid endarterectomy for patients
with stenosis of at least 60%. Observational studies support the
role of modifying lifestyle-related risk factors (eg, smoking,
alcohol use, physical activity, diet) in stroke prevention.
Measures to help patients improve adherence are an important
component of a stroke prevention plan.
Treatment
of Intermittent Claudication With Physical Training, Smoking
Cessation, Pentoxifylline, or Nafronyl : A Meta-analysis
Source: Arch Intern Med. 1999;159:337-345
Background: There is no consensus on the efficacy of physical
training, smoking cessation, and pharmacological therapy
(pentoxifylline or nafronyl oxalate) in the treatment of patients
with intermittent claudication at Fontaine stage II of disease.
Methods: A MEDLINE and manual search was used to identify
relevant publications. Uncontrolled or retrospective studies,
double reports, and trials without clinically meaningful outcomes
were excluded. Included studies were graded level 1 (randomized
and double- or assessor-blind), level 2 (open randomized), or
level 3 (nonrandomized). Pain-free and total walking distance
were the main outcomes
considered; when feasible, end-of-treatment results were combined
with appropriate meta-analytical procedures.
Results: In 5 level 2 studies, physical training increased
pain-free and total walking distance significantly (139.0 m [95%
confidence interval {CI}, 31.0 to 246.9 m] and 179.1 m [95% CI,
60.2 to 298.1 m], respectively). In a level 3 study, smoking
cessation resulted in a nonsignificant increase in total walking
distance of 46.7 m (95% CI, -19.3 to 112.7 m). In 6 level 1
studies, pentoxifylline increased both
pain-free and total walking distance by 21.0 m (95% CI, 0.7 to
41.3 m) and 43.8 m (95% CI, 14.1 to 73.6 m), respectively. In 4
level 1 trials, nafronyl significantly increased pain-free
walking distance (58.6 m [95% CI, 30.4 to 86.8 m]) and total
walking distance (71.2 m [95% CI, 13.3 to 129.0 m]).
Conclusions: Physical training increased pain-free and total
walking distance in level 2 studies. Only level 3 studies support
the usefulness of smoking cessation. In level 1 studies,
pentoxifylline and nafronyl increased pain-free and total walking
distance, but the average effects were relatively small.
