In a recent study published in the journal Nature Cardiovascular Research, researchers observe an increased risk of cardiometabolic multimorbidity (CMM) and mortality with accelerated biological aging.
Study: Accelerated biological aging elevates the risk of cardiometabolic multimorbidity and mortality. Image Credit: Explode / Shutterstock.com
What is CMM?
CMM, which is the coexistence of two or more cardiometabolic diseases
(CMDs), including ischemic heart disease (IHD), stroke, and type 2
diabetes (T2D), has been associated with reduced life expectancy and
mortality. CMM occurs due to the physiological aging of cardiometabolic
systems; therefore, reliable tools are needed to assess and predict CMM
risks for clinical management and prevention.
Biological aging measures based on clinical traits reflect the
landscape of aging across multiple organs and systems. To date, two
biological aging measures have been associated with the risk of
mortality, aggravating disability, falls, care home admission, and
hospitalization in older adults; however, their associations with CMM
dynamics remain undefined.
About the study
Researchers used health, lifestyle, and physical measurement data
from the United Kingdom Biobank participants to assess the relationship
between biological aging and CMM risk. Individuals lacking information
on CMDs, traits for biological aging measures, covariates, and those
with stroke, IHD, or T2D at baseline were excluded from the analysis.
Incident T2D, stroke, and IHD cases and mortality were determined
using self-reported, primary care, and hospitalization data. Biological
aging was quantified based on 12 blood chemistry characteristics, lung
function, and systolic blood pressure using the PhenoAge and
Klemera-Doubal method Biological Age (KDM-BA) algorithms.
Frailty was determined by the frailty phenotype, defined as five
deficits, including exhaustion, weight loss, grip strength, walking
speed, and physical activity. Cardiovascular risk was assessed using
systematic coronary risk evaluation 2 (SCORE2) and Framingham risk score
(FRS) algorithms. Covariates included age, sex, body mass index (BMI),
education, ethnicity, employment, smoking, alcohol consumption, physical
activity, and household income.
Survival time was calculated from baseline to incident event, death,
or censoring. Cox regression models examined the association of PhenoAge
and KDM-BA with first CMD (FCMD), CMM, and death, all of which were
adjusted for covariates. Unidirectional multistate models assessed
temporal disease progression among participants free of CMDs at
baseline.
Five transition states were created for pattern A, of which included
baseline to FCMD, baseline to death, FCMD to CMM, FCMD to death, and CMM
to death. FCMD was stratified into stroke, IHD, and T2D to determine
which CMD had a greater risk of CMM. This led to the creation of
sub-transitions in stages one, three, and four of pattern A, which
resulted in 11 transitions denoted as pattern B.
Study findings
A total of 341,159 individuals with an average age of 55.8 years were
included in the study. Over 95% of the study cohort were White, 53.6%
were male, 55.3% were never smokers, 62.9% were employed, 69.5% had at
least 10 years of education, and 72.1% reported high physical activity
levels. During the follow-up period, 7.71% of participants developed at
least one CMD.
A
total of 2,396 individuals had a stroke, 10,571 with T2D, and 13,352
with IHD. Moreover, 2,502 participants developed CMM, 8,508 deaths were
recorded without CMM, and 360 deaths occurred after CMM. The average
PhenoAge acceleration was -11.14 years, whereas the mean KDM-BA
acceleration was -13.81 years.
Both PhenoAge and KDM-BA acceleration estimates were associated with
the risk of FCMD, CMM, and mortality. The two measures showed
considerable associations with all stages of CMM. The adjusted hazard
ratios (HRs) with KDM-BA acceleration were 1.22, 1.14, and 1.42 for
transitions from baseline to FCMD, FCMD to CMM, and CMM to death,
respectively.
For PhenoAge acceleration, the corresponding HRs were 1.24, 1.15, and
1.26, respectively. The probability of FCMD-to-death or CMM-to-death
transition was 10-30% greater than the transition from baseline to
death. The probability of transition from FCMD to CMM was much higher
than that of baseline-to-FCMD transition.
The probability of FCMD-to-CMM transition was highest in the eighth
year for both measures. The HRs for the baseline-to-FCMD and FCMD-to-CMM
transitions for every single standard deviation increase in FRS and
SCORE2 were much lower than those of PhenoAge and KDM-BA acceleration
estimates. Moreover, the HRs for SCORE2 and FRS for other transitions
were not statistically significant.
Conclusions
Taken together, the study findings highlight that accelerated
biological aging could help identify people at risk of CMM and
mortality, thereby allowing for early intervention and sub-clinical
prevention.
Journal reference:
- Jiang, M., Tian, S., Liu, S., et al. (2024) Accelerated biological
aging elevates the risk of cardiometabolic multimorbidity and mortality.
Nature Cardiovascular Research. doi:10.1038/s44161-024-00438-8
