AIM
- To investigate the association between body mass index
(BMI) in late adolescence and death from cardiovascular disease in adulthood.
METHOD
-BMI data from 1967 through 2010 Israeli adolescents (mean
age 17.3±0.4 years)
were grouped according to age- and sex- specific percentiles from the US CDC.
[Underweight: <5th percentile
Normal weight: 5th to 24th percentile (Reference
group), 25th to 49th percentile, 50th to 74th
percentile, 75th to 85th percentile
Overweight: 85th to 94th percentile
Obese: ≥
95th percentile]
- Total number of study sample: 2,298,130 participants
- Primary outcomes: number of deaths attributed to coronary
heart disease, stroke, sudden death from unknown cause or a combination of all
three categories (total cardiovascular causes) by mid-2011.
- Statistical analysis: Cox proportional-hazards
models; imputed 1.4% of missing values (country of origin, education and
socioeconomic status) using multiple imputation algorithm; applied
linear and quadratic terms using the midpoint of each BMI percentile group or
the median of each absolute BMI group; spline models were fit to estimate the
BMI value associated with minimum cardiovascular mortality and the lowest BMI associated
with significantly increased mortality.
RESULTS
- During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were from cardiovascular
causes, including 1497 from coronary heart disease, 528 from stroke, and 893
from sudden death.
- The mean ages
at the time of death were 47.4 years for coronary heart disease, 46.0
years for stroke, and 41.3 years for sudden death
- The rates of death per person-year were generally lowest in the group that had BMI values during adolescence in the 25th
to 49th percentiles, with higher rates observed among those below the 5th
percentile.
- A graded increase
in the risk of death from
cardiovascular causes and all causes that started among participants in the
group that was in the 50th to 74th
percentiles of BMI (i.e., within the accepted normal range).
Analysis based on
percentile grouping
Hazard ratio after multivariable adjustment*
(Reference group: 5th to 24th percentile):
- Overweight (85th to 94th percentiles): 3.0 (95%
CI, 2.5-3.7) for death from coronary heart disease, 1.8 (95% CI, 1.3-2.5) for
death from stroke, 1.5 (95% CI, 1.1-1.9) for sudden death, and 2.2 (95% CI,
1.9-2.6) for death from total cardiovascular causes
-Obese group (≥95th
percentile for BMI): 4.9 (95% CI, 3.9-6.1) for death from coronary heart
disease, 2.6 (95% CI, 1.7-4.1) for death from stroke, 2.1 (95% CI, 1.5-2.9) for
sudden death and 3.5 (9.5% CI, 2.9-4.1) for death from total cardiovascular
causes
*(adjustment for sex, age, birth year,
sociodemographic characteristics, and height)
Analysis based on
year of follow-up
- Hazard ratio from death from cardiovascular disease increased
from 2.0 (95% CI 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI
3.1 to 5.4) during follow-up for for 30 to 40 years
- The risk was persistently high for death from coronary
heart disease across the entire period of follow-up.
Analysis of absolute
values of BMI
- Participants with a BMI ranging from 20.0 to 22.4 had a
higher risk of death from coronary heart disease than did those with a BMI
ranging from 17.5 to 19.9 (hazard ratio, 1.2; 95% CI, 1.1-1.4)
- The risks of death from stroke, sudden death, and total
cardiovascular causes (along with noncardiovascular causes and all causes) were
also elevated starting with a BMI of 22.5 and increased more steeply among the
extremely obese for cardiovascular-specific death
On multivariable-adjusted spline models,
-The minimum risks of death from stroke, sudden death, and
cardiovascular causes were among participants who had BMI values of 19.8, 19.3,
and 18.3, respectively, whereas the association with death from coronary artery
disease was graded across the full range of BMI-percentile groups
- Participants had a significantly elevated risk of death
from total cardiovascular causes starting at BMI values above 20.3.
Analysis by z-scores
of BMI
- After multivariable adjustment, the hazard ratios for
death from coronary heart disease were 1.54 (95% CI, 1.46 to 1.62) for men and
1.58 (95% CI, 1.31 to 1.91) for women per 1-unit increment in the z score
Sensitivity
analysis
- Findings persisted in extensive sensitivity analyses: sex-specific, restricted to adolescents with unimpaired
health status, analysis modelling the association without competing risks that used
the group with BMI values in the 25th to 49th percentiles as the reference
category, restricted to participants who were evaluated after 1981 and to those
who were evaluated from 1967 through 1980, comparing deaths that
occurred before the age of 45 years with those that occurred at the age of 45
years or older, analyses according to calendar periods of follow-up and country
of origin, and an analysis that included all cardiovascular diseases defined
according to ICD coding (9.9% of all deaths)
Analysis of
population-attributable fractions
- Among participants with a BMI higher than the 50th
percentile in 2013, the projected population-attributable fractions were 28%
for death from total cardiovascular causes and 36% for death from coronary
heart disease
DISCUSSION
- There is a graded increase in the risk of death starting
at the mid-normal range of adolescent BMI (50th to 74th percentiles) and that the high normal BMI
range (75th to 84th percentiles) was associated with hazard ratios of 2.2 for
coronary heart disease and 1.8 for total cardiovascular causes.
- Our findings appear to provide a link between the secular
trends in adolescent overweight and coronary mortality during the past decades.
In contrast to the steep decline in the rate of death from cardiovascular
causes among older age groups, cardiovascular mortality among young adults has
not decreased or the decline has slowed in several developed countries.
LIMITATIONS
- Absence of adult measures of BMI, an independent effect of
adolescent BMI on death from cardiovascular disease in adulthood cannot be
assessed.
- Unable to account for important cardiovascular lifestyle
risk factors (such as smoking, exercise, and physical fitness) that may
confound the BMI association, although adjustment for smoking had no effect in
other studies, and a mendelian randomization study showed effects for BMI that
were independent of confounding
- The study sample is less representative of Israeli women, and
the findings need to be confirmed in a racially and ethnically diverse
population
CONCLUSION
- An increased BMI in late adolescence, even within the
currently accepted normal range, was strongly associated with cardiovascular mortality
in young adulthood or midlife
- We could not determine whether an increased BMI in
adolescence is an independent risk factor, is mediated by adult obesity, or
both
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