Personalized antihypertensive treatment based on pathophysiology

Arterial hypertension remains one of the most prevalent chronic diseases worldwide and a leading risk factor for myocardial infarction, stroke, chronic heart failure, and chronic kidney disease. Despite the availability of multiple classes of antihypertensive medications, adequate blood pressure control is not achieved in a substantial proportion of patients. This limitation is largely explained by the heterogeneity of underlying pathophysiological mechanisms, genetic variability, neurohormonal differences, and the impact of coexisting medical conditions.

Targeted therapy in cardiology is based on the principle of intervening in specific pathogenic pathways responsible for disease progression. In hypertension, the major mechanisms include activation of the renin–angiotensin–aldosterone system, increased sympathetic nervous system activity, endothelial dysfunction, sodium retention with volume expansion, and structural vascular remodeling. A personalized approach requires identifying the predominant mechanism in an individual patient and selecting treatment that specifically addresses that component.

Modulation of the renin–angiotensin–aldosterone system represents a cornerstone of targeted antihypertensive therapy. In patients with increased activity of this system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are particularly effective. These agents reduce systemic vascular resistance, limit myocardial and vascular remodeling, and provide nephroprotective effects. The choice of a specific agent depends on the clinical context, including the presence of diabetic nephropathy or heart failure.

When heightened sympathetic activity is a dominant mechanism, beta-adrenergic blockers or centrally acting alpha-2 agonists may be appropriate. These medications decrease heart rate, reduce cardiac output, and suppress neurohormonal stimulation. In patients with tachycardia, ischemic heart disease, or a history of myocardial infarction, such an approach allows simultaneous blood pressure control and reduction of recurrent cardiovascular events.

Endothelial dysfunction also plays a significant role in the development of hypertension. Impaired nitric oxide production and predominance of vasoconstrictive mediators contribute to increased vascular tone. Calcium channel blockers and certain renin–angiotensin system inhibitors may improve endothelial function and reduce arterial stiffness. Risk factor modification, including management of dyslipidemia, insulin resistance, and chronic inflammation, further supports vascular health.

Pharmacogenetic research suggests that polymorphisms in genes encoding components of the renin–angiotensin system, sodium transporters, and adrenergic receptors may influence individual responses to antihypertensive therapy. Although routine genetic testing is not yet standard practice, future integration of genomic data may enhance therapeutic precision and reduce adverse drug reactions.

Assessment of arterial stiffness and central aortic pressure provides additional insight into hemodynamic patterns. Patients with pronounced vascular rigidity may benefit from medications that improve arterial compliance. Noninvasive techniques, such as pulse wave analysis, allow clinicians to characterize vascular properties and tailor therapy accordingly.

Comorbidities significantly influence therapeutic decisions. In chronic kidney disease, agents with nephroprotective properties are preferred. In diabetes mellitus, minimizing metabolic side effects and protecting target organs is essential. In patients with chronic obstructive pulmonary disease, the selection of beta-blockers requires careful consideration to avoid bronchoconstriction. Targeted therapy therefore encompasses not only the mechanism of hypertension but also the broader clinical profile.

Resistant hypertension presents a distinct clinical challenge. Comprehensive evaluation is required to exclude secondary causes, including primary aldosteronism, renal artery stenosis, and obstructive sleep apnea. Identification of specific etiologies enables targeted interventions such as mineralocorticoid receptor antagonists or interventional procedures.

Interventional approaches further expand the concept of targeted therapy. Renal sympathetic denervation has been investigated in patients with resistant hypertension associated with increased sympathetic drive. By reducing afferent and efferent renal sympathetic signaling, this procedure may contribute to sustained blood pressure reduction in carefully selected individuals.

Ambulatory blood pressure monitoring is an essential component of personalized management. Analysis of circadian patterns can reveal nocturnal hypertension, insufficient nighttime dipping, or pronounced morning surges. These characteristics influence drug selection and timing of administration, enhancing therapeutic effectiveness.

A personalized strategy integrates clinical evaluation, laboratory findings, imaging data, and, when available, genetic information. Such a comprehensive assessment enables transition from standardized treatment algorithms to individualized regimens aimed at achieving target blood pressure levels with minimal adverse effects.

In conclusion, targeted therapy in arterial hypertension reflects the broader movement toward personalized medicine. Given the complexity of blood pressure regulation and the diversity of pathogenic pathways, individualized treatment improves therapeutic efficacy, reduces complication rates, and contributes to better long-term cardiovascular outcomes.