Objective: Previous studies on the association between metabolic biomarkers and hypertension have been limited by small sample sizes, low number of studied biomarkers, and cross-sectional study design. In the largest study to date, we assess the cross-sectional and longitudinal associations between high-abundance serum biomarkers and blood pressure (BP).

Methods: We studied cross-sectional (N = 36 985; age 50.5 ± 14.2; 53.1% women) and longitudinal (N = 4197; age 49.4 ± 11.8, 55.3% women) population samples of Finnish individuals. We included 53 serum biomarkers and other detailed lipoprotein subclass measures in our analyses. We studied the associations between serum biomarkers and BP using both conventional statistical methods and a machine learning algorithm (gradient boosting) while adjusting for clinical risk factors.

Results: Fifty-one of 53 serum biomarkers were cross-sectionally related to BP (adjusted P < 0.05 for all). Conventional linear regression modeling demonstrated that LDL cholesterol, remnant cholesterol, apolipoprotein B, and acetate were positively, and HDL particle size was negatively, associated with SBP change over time (adjusted P < 0.05 for all). Adding serum biomarkers (cross-sectional root-mean-square error: 16.27 mmHg; longitudinal: 17.61 mmHg) in the model with clinical measures (cross-sectional: 16.70 mmHg; longitudinal 18.52 mmHg) improved the machine learning model fit. Glucose, albumin, triglycerides in LDL, glycerol, VLDL particle size, and acetoacetate had the highest importance scores in models related to current or future BP.

Conclusion: Our results suggest that serum lipids, and particularly LDL-derived and VLDL-derived cholesterol measures, and glucose metabolism abnormalities are associated with hypertension onset. Use of serum metabolite determination could improve identification of individuals at high risk of developing hypertension.