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Modifiable Factors Increase Risk of Young-Onset Heart Failure


Morbidity and mortality in individuals younger than 55 years with heart failure may be attenuated by targeting possible age-dependent risk factors

The incidence of heart failure is reportedly on the rise among individuals aged 65 years and younger, with reports indicating this may be the result of modifiable risk factors—despite the absolute risk for the disease still being lower in these individuals with and without risk factors.

Investigating these possible age differences in clinical phenotypes of heart failure, the authors of a recent pooled population-based cohort study recruited their 24,675 participants from 3 current studies:

  • Framingham Heart Study (n = 9877)
  • Prevention of Renal and Vascular Endstage Disease study (n = 8115)
  • Multi-Ethnic Study of Atherosclerosis (n = 6683)

The participants were grouped into 4 age-based cohorts: young (< 55 years; n = 11,599), middle aged (55-64 years; n = 5587), old (65-74 years; n = 5190), and elderly (≥ 75 years; n = 2299). Their mean (SD) age was 56 (14) years.

“Understanding age-dependent differences in risk factors leading up to development of heart failure may shed light on observed differences in clinical phenotypes across age and ultimately may inform future preventive strategies,” the authors stated.

Their findings were published in BMJ.

Over the course of the study, 5.6% of all participants developed heart failure, with the lowest incidence in the young age group (1.0%) and the greatest incidence in the elderly age group (18.0%). For the young participants, the median (interquartile range [IQR]) age of heart failure onset was 58 (IQR, 51-63) years compared with 89 (IQR, 86-92) among the elderly participants.

The younger participants also had a lower rate of heart failure with preserved ejection fraction compared with the elderly participants: 32% vs 43%. Most study participants overall (55%) developed heart failure with reduced ejection fraction.

However, certain risk factors in the younger participants did increase the risk of developing heart failure vs the elderly participants, and they are hypertension (average of 2 seated measurements), diabetes (fasting plasma glucose ≥ 126 mg/dL), current smoking history, and previous myocardial infarction:

  • Hypertension: HR of 3.02 (95% CI, 2.10-4.34) vs HR of 1.43 (95% CI, 1.13-1.81)
  • Diabetes: HR of 3.86 (95% CI, 2.39-6.23) vs HR of 1.66 (95% CI,1.24-2.24)
  • Smoking: HR of 2.58 (95% CI, 1.83-3.63) vs HR of 1.21 (95% CI, 0.80-1.83)
  • Previous myocardial infarction: HR of 3.30 (95% CI, 1.77-6.14) vs HR of 1.35 (95% CI, 0.89-2.08)

Certain risk factors, too, had higher population-attributable risks in the younger participants compared with the elderly participants:

  • Obesity (body mass index ≥ 30): 21% vs 13%
  • Hypertension : 35% vs 23%
  • Diabetes: 14% vs 7%
  • Current smoker: 32% vs 1%

These results were seen despite there being higher rates of antihypertensive treatment (10% vs 50%), diabetes (3% vs 12%), previous myocardial infarction (2% vs 4%), and atrial fibrillation (1% vs 6%) in the elderly participants.

“All risk factors were evaluated and harmonized across cohorts,” the authors noted.

In addition, known risk factors were associated with a higher overall population-attributable risk in the younger vs elderly participants (75% vs 53%) and better model performance (C index, 0.79 vs 0.64.

The authors believe their findings are important because they emphasize that heart failure prevention efforts should target younger patient populations, too, although the timeline for results in these individuals may need to be longer.

“This should take into account the potential number of disease-free life years saved,” they concluded. “A discussion on possible reasons for age-dependent association of risk factors with incident heart failure is warranted.”


Tromp J, Paniagua SMA, Lau ES, et al. Age dependent associations of risk factors with heart failure: pooled population based cohort study. BMJ. Published online March 23, 2021. doi:10.1136/bmj.n461

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