Written in
Featured research from recent issues of Blood
PAPER SPOTLIGHT
CARDIA Study: Sickle Cell Trait Is
Not Independently Associated With
Cardiovascular Disease Risk
Despite concerns that
sickle cell trait (SCT) is
associated with poor
cardiopulmonary fitness
and certain cardiovascular
risk factors, the relationship between SCT and
fitness has not been
extensively examined. In a
report published in Blood,
Robert I. Liem, MD, MS,
and authors analyzed data
from the 25-year, longitudinal CARDIA (Coronary
Artery Risk Development
in Young Adults) study to
determine if patients with
SCT were at an increased
risk for adverse cardiovascular outcomes, such
as sudden death during
strenuous physical activity
or the development of
cardiovascular disease
(CVD), compared with
those without SCT.
Dr. Liem, from the
Department of Hematology, Oncology & Stem Cell
Transplantation at Ann &
TABLE 1.
Robert H. Lurie Children’s
Hospital of Chicago, and
authors found that SCT
carrier status was not
associated with baseline
or long-term changes in
cardiopulmonary fitness.
Combined with results
from a recent population
study of African-American
active-duty soldiers in the
U.S. Army, which found
that SCT was not associated with a higher overall
risk of death (but was
associated with a higher
risk of exertional rhabdomyolysis), these findings
support the idea that SCT
status is not a risk for
adverse cardiovascular
outcomes.
“Having SCT alone
does not affect one’s
overall fitness level or
one’s risk of developing risk factors for heart
disease,” Dr. Liem told
ASH Clinical News. “However, it doesn’t mean that
individuals with SCT will
not have lower fitness
or will not develop those
complications for all of the
usual reasons that people
without SCT do.”
CARDIA included 5,115
patients (age range =
18-30 years) who were
enrolled from four U.S.
cities (Birmingham,
Alabama; Oakland, California; Chicago, Illinois; and
Minneapolis, Minnesota)
between 1985 and 1986;
patients were followed
for 25 years, with seven
examinations over the
course of the follow-up
period (at years 2, 5, 7, 10,
15, 20, and 25).
Dr. Liem and authors
restricted their analysis to
the 1,995 African-American patients enrolled
in CARDIA who had SCT
genotype information and
fitness data available at
baseline. Patients with
sickle cell disease, those
SCT and Incident CVD Risk Factors Over 25 Years
Hazard Ratio (HR)
N
HR
682/1,482
(56.9%)
Reference
56/108
(60.6%)
1.22
(95% CI 0.91-1.65)
262/1,519
(173%)
Reference
26/112
(23.2%)
1.48
(95% CI 0.96-2.27)
596/1,502
(39.7)
Reference
49/109
(45%)
1.26
(95% CI 0.92-1.74)
Incident hypertension
No SCT
SCT
Incident diabetes
No SCT
SCT
Incident metabolic syndrome
No SCT
SCT
SCT = sickle cell trait; CVD = cardiovascular disease
42
ASH Clinical News
who underwent bariatric
surgery, and those with
missing baseline covariates were excluded.
Seven percent of these
patients had confirmed
SCT – a prevalence rate
similar to the estimated
carrier rate in the United
States, the authors noted.
Mean patient age was
24.8 years for those with
SCT and 24.3 years for
those without SCT. Baseline characteristics were
similar between patients
with and without SCT,
with a similar prevalence
of hypertension, diabetes,
and metabolic syndrome
among both cohorts.
However, diastolic blood
pressure (BP) was slightly
higher in those with SCT
compared with those without SCT (71 vs. 69 mm Hg;
p=0.02).
The authors used a
graded, symptom-limited
maximal treadmill test
(Balke protocol, which
included 9 stages of increasing difficulty defined
by treadmill speed and
incline) during the year
7 and year 20 exams to
assess fitness. Seated
BP, cholesterol, height,
weight, waist circumference, and physical activity
were also assessed after a
12-hour fast. Demographic
information, physical
activity, and medication
use were recorded via an
interview-administered
questionnaire.
No significant differences were observed in
baseline fitness parameters (including mean duration of exercise, maximum
heart rate achieved, and
heart rate at 2 minutes
of recovery), even after
adjusting for sex, baseline
age, body mass index,
and physical activity, the
authors noted. Long-term
follow-up also showed no
significant difference in
annual change in graded
exercise performance between patients with and
without SCT status.
Those with and
without SCT had a similar
risk of developing the following cardiovascular risk
factors during the 25-year,
follow-up period:
• hypertension (defined as
systolic BP ≥140 mm Hg,
diastolic BP ≥90 mm
Hg, or those who were
taking antihypertensive
medication; p=0.19)
• diabetes (defined
as fasting glucose
≥126 mg/dL, glycated
hemoglobin >6.5
percent, post-load
glucose ≥200 mg/dL, or
those who were taking
diabetes medication;
p=0.08)
• metabolic syndrome
(defined as presence of
diabetes or hypertension, increased waist
circumference, triglycerides ≥150 mg/dL or
those who were taking
cholesterol medication;
p=0.15)
See TABLE 1 for more
detailed results about
the risks of developing
incident CVD risk factors
in each study cohort.
“Our findings suggest that SCT status
alone probably does not
explain the racial disparities in fitness observed
between African Americans and non−African
Americans, given that
we found no difference
in fitness by SCT status,”
the authors wrote.
Dr. Liem noted that
December 2016