Environmental extreme heat exposure and blood pressure dysregulation in older hypertensive adults: Metabolomic evidence for biological plausibility.

Extreme heat events are intensifying under climate change, yet pathways linking heat exposure to blood pressure (BP) dysregulation in older hypertensive adults remain poorly defined. Here, we conducted a repeated-measures cohort study among 40 older adults (median age: 67.0 years) with hypertension in Tianjin, China, collecting BP measurements and fasting venous blood samples at baseline (June 2023; daily maximum temperature 24 °C) and following the first official heatwave warning (July 2023; 38 °C). High-temperature exposure was associated with significant increases in systolic BP (SBP: +11.90 mm Hg, 95% confidence interval [CI]: 6.89-16.91; P < 0.001), diastolic BP (DBP: +7.00 mm Hg, 95% CI: 4.67-9.33; P < 0.001), mean arterial pressure (MAP: +8.63 mm Hg, 95% CI: 6.22-11.04; P < 0.001), and pulse pressure (PP: +2.88 mm Hg, 95% CI: 1.50-4.26; P < 0.001). Untargeted serum metabolomics via ultra-high-performance liquid chromatography-quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) identified 29 significantly altered metabolites among 314 profiled (|log2FC| > 1.5, adjusted P < 0.05), with pathway enrichment implicating the citrate cycle, pyruvate metabolism, and nicotinate and nicotinamide metabolism. Integrative analysis intersecting heat-responsive and BP-associated metabolites identified six candidate metabolomic biomarkers-glycolate, azelate, adenosine monophosphate (AMP), inosine, N-carbamoyl-L-aspartate, and dihydroorotate-converging on pyrimidine metabolism, purine metabolism, and alanine, aspartate and glutamate metabolism. These findings provide hypothesis-generating metabolomic evidence supporting the biological plausibility that extreme heat may perturb metabolic pathways associated with clinically meaningful BP elevations in older hypertensive adults, with potential implications for environmental health risk assessment and heat-health warning strategies for climate-vulnerable populations.