Plasma ceramides independently predict all-cause mortality in men aged 85
Timo E Strandberg1,2,3, Mika Kivimäki1,4, Annele Urtamo1
1Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Insights
Plasma ceramides, a type of lipid, may serve as a valuable biomarker for predicting mortality risk in the oldest-old individuals. This finding is crucial for improving geriatric care where conventional methods are less effective.
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.
Background:
assessing cardiovascular and mortality risk with conventional biomarkers is challenging in oldest-old due to multimorbidity and polypharmacy. Ceramides are bioactive lipids shown to predict mortality in late middle-aged cohorts.
Objective:
to assess whether plasma ceramides have independent prognostic value for mortality among oldest-old (85+).
Design:
longitudinal cohort study (Helsinki Businessmen Study, HBS) with a 3.5-year follow-up.
Setting And Subjects:
survivors of HBS (125 men born in 1919-1934) visited the clinic for laboratory and clinical examination.
Methods:
functional status including physical (short physical performance battery) and Montreal Cognitive Assessment (MoCA) cognitive performance was assessed and laboratory examinations included a large set of biomarkers. Plasma ceramide concentration (Cer(d18:1/16:0)) was measured using a targeted liquid chromatography-tandem mass spectrometry assay. Mortality was retrieved from national registers.
Results:
median age was 88 years, two-thirds had multimorbidity and 59% were on statin treatment. During the follow-up, 22 (18%) men died. In a model adjusted for variables associated with mortality in the whole cohort at P < 0.20 (log glucose, SPPB, MoCA and statin use), Cer(d18:1/16:0) as a continuous trait was associated with increased mortality: hazard ratio (HR) per 1 SD 1.64 (95% confidence interval [CI] 1.23-2.18). Compared with the bottom tertile of Cer(d18:1/16:0), HR of mortality was 5.44-fold (95% CI 1.17-25.3) in the top tertile.
Conclusions:
these data raise the hypothesis that plasma ceramide concentrations and especially Cer(d18:1/1:60) may offer a clinically useful biomarker to evaluate prognosis in very old age. Such biomarkers are needed for geriatrics, where multimorbidity and pharmacotherapies, such as statins are prevalent hampering assessment of prognosis using conventional methods.
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