Having a body mass index (BMI) between the 50th and 74th percentiles during adolescence was associated with an increased risk of cardiovascular (CV) and all-cause mortality, according to data published in the New England Journal of Medicine.

Researchers gathered BMI data from 2.3 million Israeli adolescents between 1967 through 2010 (mean age: 17.3 ± 0.4 years). They set the primary outcomes as number of deaths related to coronary heart disease (CHD), stroke, sudden death from an unknown cause, or a combination of all 3 categories by mid-2011.

Of the total number of deaths (32 127), 2918 were from CV causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death, which occurred during 42 297 007 person-years of follow-up. Researchers discovered a graded increase in death risk from CV causes and all causes on multivariable analysis. This increase began in the patients between the 50th and 74th BMI percentiles (ie, “within the accepted normal range”).


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The obese group (≥95th percentile for BMI) compared with the reference group (5th to 24th percentiles for BMI) had hazard ratios of 4.9 (95% confidence interval [CI]: 3.9-6.1) for death from CHD, 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 (95% CI: 2.9-4.1) for death from total CV causes. These hazard ratios (HR) were determined after adjustment for sex, age, birth year, sociodemographic characteristics, and height.

In the same percentile groups, HRs for death from CV causes increased from 2.0 (95% CI: 1:1-3.9) during follow-up for 0 to 10 years to 4.1 (95% CI: 3.1-5.4) during follow-up for 30 to 40 years. Death from CHD also had consistently high HRs during follow-up.

In the BMI group categorized as overweight (85th to 94th percentiles), individuals had HRs of 3.0 (95% CI: 2.5-3.7) for death from CHD, 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 CV causes. HRs among all categories of death were generally lowest in the 25th to 49th or 5th to 24th BMI percentiles.

Individuals with BMIs ranging from 20.0 to 22.4 had a higher risk of death from CHD than those with BMIs ranging from 17.5 to 19.9 (HR: 1.2; 95% CI: 1.1-1.4) in the analysis of absolute values of BMI. At a BMI of 22.5, risks of death (from stroke, sudden death, and total CV causes along with non-CV causes) began to elevate and rose steeply among the extremely obese individuals for CV-specific death.

“Our findings appear to provide a link between the secular trends in adolescent overweight and coronary mortality during the past decades,” the researchers wrote. “In contrast to the steep decline in the rate of death from CV causes among older age groups, CV mortality among young adults has not decreased or the decline has slowed in several developed countries.”

Researchers considered 2 possible pathways by which adolescent BMI might influence CV outcomes in adulthood. For one, obesity is marked as “deleterious” during adolescence and also associated with unfavorable metabolic abnormalities, cardiac remodeling, QT interval lengthening and coronary and aortic atherosclerotic plaque formation.

The second pathway may involve the association between adult BMI and CVD, which is supported by a Mendelian randomization study2, and may explain the association between seemingly normal BMI levels (50th to 74th percentiles) and death from total CV causes and the association between a BMI of >20.0 and death from CHD. “In the absence of adult measures of BMI,” the researchers explained, “we were unable to address this question.

“In conclusion, an increased BMI in late adolescence, even within the currently accepted normal range, was strongly associated with CV mortality in young adulthood or midlife,” they wrote. “We could not determine whether an increased BMI in adolescence is an independent risk factor, is mediated by adult obesity, or both.”

References

  1. Twig G, Yaniv G, Levine H, et al. Body mass index in 2.3 million adolescents and cardiovascular death in adulthood. N Engl J Med. 2016. doi: 10.1056/NEJMoa1503840.
  2. Hägg S, Fall T, Pioner A, et al. Adiposity as a cause of cardiovascular disease: a Mendelian randomization study. Int J Epidemiol. 2015;44(2):578-586. doi: 10.1093/ije/dyv094.