The second endotype, cytokine release endotype, is distinguished by constitutional symptoms (e.g., fever, chills, rigors, headache), cardiovascular involvement (e.g., tachycardia, hypertension or hypotension), and truncal and limb musculoskeletal pain, suggesting a cytokine-mediated response rather than IgE-mediated. This evidence concerns the gene IGHE and hypertensive disorder.