Domain

Biomarkers

Measurable physiological markers — blood pressure, resting heart rate, kidney and liver function, muscle mass — with well-established, graded associations with mortality.

Body Mass Index (BMI)Resting Heart rateBlood PressureMuscle massHeart Rate VariabilityKidney Function (eGFR)Liver Function (GGT)
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7 results

Low skeletal muscle mass index and all-cause mortality risk in adults: A systematic review and meta-analysis of prospective cohort studies

Strong
Muscle massMeta-analysisObservational evidenceSystematic review
Systematic review & meta-analysis
Low skeletal muscle mass index associated with 57% higher all-cause mortality risk (pooled RR 1.57, 95% CI 1.25–1.96) across 16 prospective studies, 81,358 participants
Causal status: Associational; prospective cohort evidence, biologically plausible via frailty/functional decline pathway
Reliability / bias notes: Heterogeneous SMI definitions across studies; risk magnitude varies substantially by BMI subgroup
Wang et al · PLoS One · 2023 · PMID 37285331
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BMI and all-cause mortality: IPD meta-analysis of 239 prospective studies

Strong
Body Mass Index (BMI)Meta-analysisObservational evidenceReverse causation risk
Meta-analysis
Vs BMI 22.5–<25: obesity 30–<35 HR 1.45; 35–<40 HR 1.94; 40–<60 HR 2.76
Causal status: Predominantly association; causal contribution plausible
Reliability / bias notes: Muscle mass and fat distribution; low-BMI reverse causation
Global BMI Mortality Collaboration · Lancet · 2016 · PMID 27423262
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Blood pressure lowering for prevention of cardiovascular disease and death: systematic review and meta-analysis

Strongest tier
Blood PressureInterventional / RCT evidenceMeta-analysisSystematic review
Systematic review & meta-analysis
~10 mmHg SBP lowering in RCT meta-analysis reduced all-cause mortality RR 0.87; observational 20 mmHg higher usual SBP materially increased vascular mortality
Causal status: Strong randomized/interventional evidence
Reliability / bias notes: Treatment status, age, white-coat effect, overtreatment; lower is not always better
Ettehad et al · Lancet · 2016 · PMID 26724178
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Gamma-glutamyltransferase is associated with cardiovascular and all-cause mortality: a meta-analysis of prospective cohort studies

Moderate
Liver Function (GGT)Meta-analysisObservational evidence
Meta-analysis
Highest vs lowest GGT quartile associated with 56% higher all-cause mortality (pooled RR 1.56, 95% CI 1.34–1.83) across 7 prospective cohorts, 273,141 participants
Causal status: Associational; proposed independent of alcohol intake but mechanism as a general oxidative-stress/liver marker not fully causal
Reliability / bias notes: GGT is nonspecific (affected by alcohol, medications, fatty liver); Asian subgroup result not significant
Du et al · Prev Med · 2013 · PMID 23571185
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Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

Strong
Kidney Function (eGFR)Confounding riskObservational evidence
Observational study
Adjusted death risk rose stepwise as eGFR fell below 60 mL/min/1.73m2, from HR 1.2 (eGFR 45–59) up to HR 5.9 (eGFR <15), in a cohort of 1.12 million adults
Causal status: Causal support strong; graded, dose-dependent association independent of comorbidities
Reliability / bias notes: Single-measurement creatinine-based eGFR; residual confounding by unmeasured comorbidity possible
Go et al · N Engl J Med · 2004 · PMID 15385656
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Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study

Moderate
Heart Rate VariabilityObservational evidence
Cohort study
1-SD decrement in low-frequency HRV power associated with 1.70x greater all-cause mortality hazard (95% CI 1.37–2.09) over 4 years in an elderly community cohort
Causal status: Associational; reflects autonomic dysfunction, prognostic value shown independent of traditional risk factors
Reliability / bias notes: Older, smaller cohort (n=736, 74 deaths); short 2-hour ECG recording window; results in elderly may not generalize to younger adults
Tsuji et al · Circulation · 1994 · PMID 8044959
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