Inflammation and oxidative stress are associated with major adverse cardiovascular events in adults with preclinical hypertension

Abstract

Inflammation and oxidative stress increase with rising blood pressure. Adults with preclinical hypertension (systolic 120–129 mmHg) have a heightened risk of major adverse cardiovascular events (MACE). However, it remains unclear whether inflammation and oxidative stress contribute to MACE risk in this population. We conducted an observational study involving 5405 adults in the Framingham Offspring and Generation III cohorts. Exclusion criteria were anti-hypertensive therapy, history of cardiovascular disease, estimated glomerular filtration rate below 60 ml/min/1.73 m2, and type-2 diabetes. Blood pressure categories were defined using the American Heart Association blood pressure criteria as normal, elevated (preclinical hypertension), stage 1, and stage 2. MACE was a composite outcome of incident coronary artery disease, stroke, and all-cause mortality. C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, intracellular adhesion molecule-1, fibrinogen, P-selectin, tumor necrosis factor-alpha receptor 2, lipoprotein-associated phospholipase A2 mass and activity, osteoprotegerin, and urinary isoprostanes increased across blood pressure categories (P < 0.001). In stepwise-selected Cox proportional hazards models, a 10-year increase in age (HR [95% CI], 3.46 [2.66,4.51]; P < 0.001), current smoking (HR [95% CI], 2.17 [1.08,4.39]; P = 0.030), a 10 mg/dL increase in low-density lipoprotein (HR [95% CI], 1.17 [1.09,1.27]; P < 0.001), interleukin-6 (HR [95% CI], 1.62 [1.25, 2.09]; P < 0.001), and urinary isoprostanes (HR [95% CI], 1.39 [1.03, 1.88]; P = 0.033) were associated with higher MACE, while female sex (HR [95% CI], 0.58 [0.37,0.95]; P = 0.028) was associated with lower MACE among adults with preclinical hypertension. Interleukin-6 and urinary isoprostanes are associated with MACE in adults with preclinical hypertension.