Inflammation in Adolescence Linked to
Early Mortality

Nicola M. Parry, DVM

September 03, 2019

Inflammation during late adolescence may be associated with early death from cancer and cardiovascular disease (CVD), a large study published online today in JAMA Pediatrics has shown.

"While the exact underlying mechanisms are unclear, inflammation has been implicated in the development of both cancer and atherosclerosis, and these data highlight the existence of detectable markers of premature mortality at an early stage of life," write Elizabeth D. Kantor, PhD, MPH, from Memorial Sloan Kettering Cancer Center, New York City, and colleagues.

While evidence has linked inflammation to certain diseases, such as cancer and CVD, less is known about the long-term consequences of early inflammation.

In their study, Kantor and colleagues investigated the potential link between inflammation in late adolescence and death.

Their study included 106,120 seemingly healthy men who had undergone medical examination to assess their ability to carry out military service. Of these, 105,460 (99.4%) were aged 18 to 20 years at the time of examination.

The investigators used erythrocyte sedimentation rate (ESR) data as a nonspecific marker of inflammation. These measurements were obtained only once, at the time of each man’s physical examination.

They categorized ESR as low (≤10 mm/h), moderate (>10 to <15 mm/h), or high (≥15 mm/h).

"[T]he threshold from moderate to high ESR corresponds to the clinical cutoff for normal ESR among adolescents and men in this age group," the authors note.

During a mean follow-up of 35 years (maximum age 57 years), 4835 of the men died.  

Underlying causes of death included cancer (n = 1105), CVD (n = 874), alcohol or drugs (n = 280), and suicide, traffic accidents, or falls (n = 1502).

After adjusting for potential confounders including age, erythrocyte volume fraction, household crowding, systolic and diastolic blood pressure, muscular strength, physical working capacity, cognitive function, and body mass index, ESR was associated with overall mortality (high vs low ESR: multivariable-adjusted hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.11 - 1.67; P for trend < .001).

ESR was also linked to death from cancer (HR, 1.78; 95% CI, 1.23 - 2.59; P for trend = .002) and CVD (HR, 1.54; 95% CI, 0.97 - 2.43; P for trend = .006).

However, there was no statistically significant association between ESR and death from alcohol or drugs (P for trend = .61) or suicide, traffic accidents, or falls (P for trend = .89).

Each man underwent ESR measurement only once; therefore, the investigators were unable to examine the potential implications of inflammation at other time points during the study.

The researchers also recognize that these findings may not be generalizable to women.

"Results suggest that ESR among ostensibly healthy men in late adolescence marks something beyond that captured by manifested adolescent health conditions," conclude Kantor and colleagues.

The findings highlight the need to better understand how subclinical inflammation in early life impacts health outcomes later, they add.

This study was supported by Örebro University Strategic Funding, the UK Economic and Social Research Council, the National Cancer Institute, and the Rose Traveling Fellowship from the Harvard T. H. Chan School of Public Health. The authors have disclosed no relevant financial relationships.

JAMA Pediatr. Published online September 3, 2019. Research Letter

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