Future Treatments and Targets for Hypertension

Data from the Conduit Artery Function Endpoint (CAFE) study showed that different classes of antihypertensive drugs have different effects on brachial versus central aortic systolic and pulse pressures and that central pressures may be a better predictor of cardiovascular outcomes in response to treatment. The Strong Heart Study also showed that central aortic pressures may be a better predictor of target end-organ damage and outcomes than are conventional brachial pressures.

Thus, it is worth mentioning several other drugs, such as soluble guanylate cyclase activators, that would lower central aortic pressures. These increase cyclic guanosine monophosphate levels in target tissues, resulting in vasodilation and an antiproliferative effect. One study found that such an activator lowered BP and inhibited cardiac hypertrophy in rats with angiotensin II–induced hypertension. This drug may also potentially reduce large-artery stiffness, lowering central aortic systolic pressures beyond the benefits observed on brachial BP.

Other experimental agents, known as advanced glycation cross-link breakers, target vascular wall thickness and its effects on BP. We know that increased large-artery stiffness occurs with aging and disease and is associated with increased brachial systolic pressure. This increased pressure is due to the accumulation of advanced glycation end products (AGEs) within the vascular wall. AGEs also impair endothelial function, leading to arterial stiffness. Therefore, targeting these molecules to reduce their levels or indeed their presence in vascular walls may have an effect on decreasing vessel stiffness and lowering BP.

Other intriguing studies have involved attempts to develop a vaccine for hypertension and the use of acupuncture in treatment of hypertension. Nonpharmacologic device-based therapies are being investigated to treat resistant hypertension, including renal denervation, baroreflex activation therapy, carotid body ablation, central iliac arteriovenous anastomosis, deep brain stimulation, median nerve stimulation, and vagal nerve stimulation. Catheter-based radiofrequency ablation of the renal sympathetic nerves can lower BP in patients with resistant hypertension. The initial results look promising, but it is not yet known whether the antihypertensive effect of radiofrequency ablation is due in part to improved patient adherence to the medication regimen. These techniques have been found to be of limited efficacy. Long-term data regarding these modalities are still lacking.

• Ng FL, Saxena M, Mahfoud F, Pathak A, Lobo MD. Device-based therapy for hypertension. Curr Hypertens Rep. 2016;18(8):61.

  Williams B, Lacy PS, Thom SM, et al; CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; CAFE Steering Committee and Writing Committee. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113(9):1213–1225.

Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.