Thursday, June 23, 2016

Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood

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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