Aging too quickly? Biological clock linked to heart disease and early death

By Tarun Sai LomteReviewed by Benedette Cuffari, M.Sc.Mar 4 2024

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.