Clinical biomarkers and associations with healthspan and lifespan: Evidence from observational and genetic data.

Background: Biomarker-disease relationships are extensively investigated. However, associations between common clinical biomarkers and healthspan, the disease-free lifespan, are largely unknown. We aimed to explore the predictive values of ten biomarkers on healthspan and lifespan, and to identify putative causal mechanisms.

Methods: Using data from 12,098 Swedish individuals aged 47-94 years, we examined both serum concentrations and genetically predicted levels of ten glycemic, lipid-, inflammatory, and hematological biomarkers. During a follow-up period of up to 16 years, 3681 incident cases of any chronic disease (i.e., end of healthspan) and 2674 deaths (i.e., end of lifespan) were documented. Cox regression models were applied to estimate the associations of a one standard deviation increase in biomarkers with healthspan and lifespan.

Findings: Seven out of ten serum biomarkers were significantly associated with risks of any chronic disease and death; elevated glycemic biomarkers and high-density lipoprotein-related biomarkers showed the strongest detrimental (hazard ratio [HR] 1·29 [95% CI 1·24-1·34]) and protective effects (HR 0·92 [95% CI 0·89-0·96]), respectively. Genetic predisposition to elevated fasting blood glucose (FBG) was associated with increased risks of any chronic disease (HR 1·05 [95% CI 1·02-1·09]); genetically determined higher C-reactive protein correlated with lower death risks (HR 0·91 [95% CI 0·87-0·95]). Notably, the genetically proxied FBG-healthspan association was largely explained by serum FBG concentration.

Interpretation: Circulating concentrations of glycemic, lipid-, and inflammatory biomarkers are predictive of healthspan and lifespan. Glucose control is a putative causal mechanism and a potential intervention target for healthspan maintenance.

Funding: This study was supported by the Swedish Research Council (2015-03,255, 2018-02,077), FORTE (2013-2292), the Loo & Hans Osterman Foundation, the Foundation for Geriatric Diseases, the Magnus Bergwall Foundation, the Strategic Research Program in Epidemiology at Karolinska Institutet (SH, JJ), the China Scholarship Council, and the Swedish National Graduate School for Competitive Science on Ageing and Health. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding as an infrastructure through the Swedish Research Council, 2017-00,641.