Abstract Cardiovascular diseases are associated with high morbidity and mortality worldwide and have several risk factors, including dyslipidemia, smoking, and hypertension. Studies have evaluated isolated risk factors in experimental models of cardiovascular disease, but few preclinical studies have assessed associations between multiple risk factors. In the present study, hypertensive Wistar rats (Goldblatt 2K1C model) received a 0.5% cholesterol diet and were exposed to tobacco smoke for 8 weeks. During the last 4 weeks, the animals were treated with vehicle, an ethanol-soluble fraction of B. trimera (30, 100, and 300 mg/kg), or simvastatin + enalapril. A group of normotensive, non-dyslipidemic, and non-smoking rats was treated with vehicle. The levels of aspartate aminotransferase, alanine aminotransferase, urea, creatinine, and hepatic and fecal lipids, blood pressure, and mesenteric arterial bed reactivity were evaluated. Cardiac, hepatic, and renal histopathology and tecidual redox state were also investigated. Untreated animals exhibited significant changes in blood pressure, lipid profile, and biomarkers of heart, liver, and kidney damage. Treatment with B. trimera reversed these changes, with effects that were similar to simvastatin + enalapril. These findings suggest that B. trimera may be promising for the treatment of cardiovascular and hepatic disorders, especially disorders that are associated with multiple risk factors.