Plasma ceramides independently predict all-cause mortality in men aged 85

Area of Science:

• Biochemistry
• Gerontology
• Cardiovascular Research

Background:

• Assessing mortality risk in the oldest-old is complex due to multimorbidity and polypharmacy.
• Conventional biomarkers are often insufficient for predicting outcomes in this population.
• Ceramides, bioactive lipids, have shown potential in predicting mortality in middle-aged cohorts.

Purpose of the Study:

• To determine if plasma ceramide levels independently predict mortality in individuals aged 85 and older.
• To explore novel biomarkers for geriatric prognostication.

Main Methods:

• Longitudinal cohort study (Helsinki Businessmen Study) with 3.5-year follow-up.
• Inclusion of 125 male survivors (born 1919-1934) with assessments of functional status (SPPB, MoCA) and biomarkers.
• Measurement of plasma ceramide (Cer(d18:1/16:0)) using liquid chromatography-tandem mass spectrometry; mortality data from national registers.

Main Results:

• The cohort's median age was 88 years, with high prevalence of multimorbidity and statin use.
• Plasma ceramide (Cer(d18:1/16:0)) concentration was independently associated with increased mortality risk (HR per 1 SD: 1.64).
• Individuals in the top tertile of ceramide levels had a 5.44-fold higher mortality risk compared to the bottom tertile.

Conclusions:

• Plasma ceramide concentrations, particularly Cer(d18:1/16:0), may serve as a clinically useful prognostic biomarker in very old age.
• These findings address the need for improved prognostic tools in geriatrics, considering multimorbidity and polypharmacy.
• Ceramides offer a potential alternative to conventional biomarkers hampered by complex patient factors.