A population-based study in Israel found that people with a high body mass index (BMI) in late adolescence had an increased risk of death from cardiovascular causes in adulthood compared with adolescents with a lower BMI.

Lead researcher Gilad Twig, MD, PhD, of Sheba Medical Center in Israel, and colleagues published their findings online in the New England Journal of Medicine on April 13.

This study included 2,298,130 Israeli adolescents between the ages of 16 and 19 who underwent a required medical evaluation from Jan. 1, 1967, to Dec. 31, 2010.

The mean age was 17.3 years old, and 85 percent of participants were born in Israel. In addition, 75 percent completed high school, and low socioeconomic status was more prevalent among underweight and obese participants.

During the follow-up period, which lasted from 1981 through 2011, 9.1 percent of the 32,127 deaths were from cardiovascular causes, including 1,497 deaths from coronary heart disease, 528 deaths from stroke and 893 deaths from sudden death from an unknown cause. The mean ages at the time of death were 47.4 years for coronary heart disease, 46 years for stroke and 41.3 years for sudden death.

The researchers found that the rates of death per person-year were typically lowest in participants with a BMI during adolescence in the 25^th to 49^th percentiles. Higher rates were observed among participants below the 5^th percentile.

After adjusting for multiple variables, the risk of death from coronary heart disease, total cardiovascular causes, noncardiovascular causes and all causes were significantly higher in adolescents with BMI values in the 50^th to 74^th percentiles compares with those in the 5^th to 24^th percentiles. The researchers also said there were graded increases in the risk of death from all cardiovascular causes as BMI percentile levels increased above the 50^th to 74^th percentiles.

A multivariable adjustment found obesity was associated with hazard ratios of 4.9 for death from coronary heart disease, 2.6 for death from stroke, 2.1 for sudden death from unknown causes, 3.5 for death from total cardiovascular causes, 1.5 for death from noncardiovascular causes and 1.7 for death from all causes.

“Obesity during adolescence was associated with a substantially increased risk of cardiovascular outcomes in middle age, particularly death from coronary heart disease,” the researchers wrote. “The associations, which were similarly evident in both sexes, persisted strongly for cardiovascular deaths occurring during four decades after the measurement of BMI in adolescence. The association withstood a series of sensitivity analyses. The population-attributable fractions in our study are projected to rise with the secular shift in the BMI distribution and indicate that overweight and obesity in adolescence may account for a fifth of cardiovascular deaths and a quarter of deaths from coronary heart disease by the time the participants reach midlife.”

The researchers cited a few limitations of the study, including that they could not assess an independent effect of adolescent BMI on death from cardiovascular disease in adulthood and could not determined whether BMI was associated with the incidence of cardiovascular disease, death from cardiovascular disease or both. They also did not have cause-specific data for 6.8 percent of all deaths, and they could not account for important cardiovascular lifestyle risk factors that may confound the BMI association. In addition, they said the sample was less representative of Israeli women than men, so the findings must be confirmed in a racially and ethnically diverse population.

“We could not determine whether an increased BMI in adolescence is an independent risk factor, is mediated by adult obesity, or both,” the researchers wrote. “The secular shift to the right in the distribution of adolescent BMI and the rising prevalence of overweight and obesity among adolescents may account for a substantial and increasing future burden of cardiovascular disease, particularly coronary heart disease.”