Personalized Medicine for High Blood Pressure

"One important characteristic of biology is its diversity, its variation. It’s why personalized medicine is so important."

Personalized medicine refers to the use of diagnostic and screening methods that exploit knowledge of the patient’s unique molecular or risk profile to achieve optimal health and medical outcome through improved management of the patient’s disease or predisposition toward a disease. High blood pressure (hypertension) is the most common modifiable risk factor for vascular disease, which in turn accounts for more morbidity and mortality than any other category of disease. This invited review attempts to explain why individualized approaches are imperative to improve the detection, evaluation, treatment, and prevention of hypertension; to recount the history of the pursuit of this "holy grail"; and to propose approaches to overcoming the many obstacles to realization of personalized medicine for hypertension.

Rationale for Personalized Medicine for Hypertension

Ischemia of vital organs, especially the brain, heart, and kidneys, causes most of the morbidity and mortality associated with hypertension. Arteriosclerosis is the disease process, encompassing two main patterns, atherosclerosis and arteriolosclerosis, that contribute to thickening of arterial walls, reduction of lumen diameters, and impairment of blood supply leading to ischemia, dysfunction, and ultimately failure of target organs. Because increased resistance to blood flow, ie, the primary vascular disorder of hypertension, involves medial thickening and consequent luminal narrowing in small, muscular arteries and end-arterioles, hypertension emerges as the strongest risk factor, after age, for arteriolosclerotic manifestations of target organ complications.

History of Personalized Medicine for Hypertension

Appreciation of the need for individualization of hypertension care is documented in the Joint National Committee (JNC) Reports on the Detection, Evaluation, and Treatment of High Blood Pressure. In the 1970s, secondary causes of hypertension were recognized to require different diagnostic and therapeutic approaches. The remaining majority of cases of so-called "essential hypertension" had been described by Page as a "mosaic" of heterogeneous mechanisms contributing to the elevation of blood pressure. Furthermore, Guyton and colleagues modeled the redundant and counterbalancing multiplicity of physiological and biochemical systems interacting to regulate blood pressure, long before "systems biology" came into vogue. Although blood pressure lowering in response to mono or combination drug therapies had been shown to differ widely among individuals, the first JNC report in 1977 recommended that the initial diagnostic evaluation be limited to patient history and physical examination. Notwithstanding the admonition that "all patients must receive individualized therapy programs," a standardized, stepped-care approach to treatment was advocated for all patients, beginning with a thiazide diuretic. The measured patient characteristics, namely, blood pressure levels, age and sex, race, presence of target organ damage (eg, left ventricular hypertrophy), and comorbidities (eg, diabetes) were considered in the decision whether to initiate drug therapy, not drug selection. Moreover, there was no discussion of matching of drug mechanism of action to the mechanism of blood pressure elevation.