The association between frailty biomarkers and 20-year all-cause and cardiovascular mortality among community-dwelling older adults

ABSTRACT

Objectives

While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty.

Methods

Nine hundred and sixty-three older adults were screened during the third phase (1999–2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH). Frailty was defined as sedentary individuals, past 10 years hospitalizations, or at least one of the following: body mass index (BMI) <21 kg/m²; albumin <3.2 g/dl; ≥2 major baseline diseases. Biomarkers were evaluated for their association with frailty, all-cause, and cardiovascular mortality.

Results

Mean baseline age was 72 ± 7 years, 471 (49%) were women, and 195 (20%) were classified as frail. Median follow-up for cardiovascular and all-cause mortality was 11 and 13 years, with 179 (18.6%) and 466 (48.4%) deaths recorded, respectively. Multivariable logistic regression showed greater odds for frailty with lower quartile of alanine aminotransferase (ALT) (OR = 1.8, 95%CI: 1.2–2.8, p = 0.01), and for each 5 µmol/L increment in homocysteine levels (OR = 1.3, 95%CI: 1.1–1.5, p = 0.001). Multivariate Cox regression showed greater all-cause and cardiovascular mortality risk for individuals with low ALT (HR = 1.6, 95%CI: 1.3–2.0, p < 0.001 and HR = 1.5, 95% CI: 1.0–2.2, p = 0.03, respectively), and high homocysteine (HR = 1.1, 95%CI: 1.1–1.3, p = 0.003 and HR = 1.2, 95%CI: 1.0–1.3, p = 0.04, respectively). Homocysteine association with mortality was more pronounced in those with baseline ischemic heart disease (IHD) compared with subjects free of IHD (P for interaction = 0.01).

Conclusions

Lower ALT and higher homocysteine were associated with frailty, all-cause and cardiovascular mortality. These available and low-cost biomarkers underscore the nutritional and metabolic aspects of frailty when screening high-risk older adults, especially those with IHD, and may be considered as preferable screening biomarkers to be tested among these individuals for frailty and mortality risk.

KEYWORDS:

• All-cause mortality
• cardiovascular mortality
• frailty
• homocysteine
• alanine aminotransferase

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Y Moshkovits contributed to the data analysis, the interpretation of data and drafting of the manuscript. R Dankner and A Chetrit contributed to the acquisition of the data, the conception and design of the work, the data analysis and drafting of the manuscript. A Chetrit and R Dankner critically revised the manuscript. All gave final approval and agreed to be accountable for all aspects of the work, ensuring integrity and accuracy.

Data availability statement

Data including the total database will be fully disclosed upon reasonable request to the corresponding author.

Ethics statement

Participants signed an informed consent to participate in the study before screening. The protocol was approved by the Sheba Medical Center’s IRB (IRB request number −1180).

Additional information

Funding

This paper was not funded.