Treating Hypertension: Modern Strategies and Clinical Challenges

Arterial hypertension, often called the “silent killer,” remains one of the leading public-health challenges of the 21st century. Despite the availability of effective therapies, blood pressure (BP) control globally remains unsatisfactory. Recent data indicate that fewer than 25% of patients achieve target BP values, highlighting the complexity of the problem, which includes clinical inertia, poor patient adherence, and insufficient health literacy.

Pathophysiological Basis and Diagnostic Approach

Most patients (90–95%) have primary, or essential, hypertension arising from a complex interaction of genetic predisposition and environmental factors such as obesity, salt intake, stress, and physical inactivity. Secondary hypertension, though less common, must be ruled out in atypical cases or resistant hypertension, particularly in younger patients.

Accurate diagnosis requires standardized BP measurement; 24-hour ambulatory blood pressure monitoring (ABPM) and home BP monitoring. Laboratory evaluation includes assessment of renal function, glucose and lipid metabolism, and evaluation of target-organ function.

Non-pharmacological Measures

Non-pharmacological interventions should be the initial and ongoing component of hypertension management at all stages and in all patients. Their effectiveness is scientifically proven and recommended in all international guidelines.

Recommended measures and effects:

• Reduce salt intake: <2.3 g sodium/day (ideally <1.5 g); BP reduction ~5–6 mmHg.

• DASH diet (Dietary Approaches to Stop Hypertension): rich in fruits, vegetables, whole grains; low in saturated fats; BP reduction ~8–14 mmHg.

• Physical activity: at least 30 minutes of moderate activity most days (e.g., brisk walking); BP reduction ~4–9 mmHg.

• Weight loss: each kilogram lost may reduce BP by ~1 mmHg.

• Limit alcohol intake: up to 2 drinks/day for men and 1 drink/day for women (a standard drink ≈ 10 g ethanol, e.g., 100 ml wine, 250 ml beer, 30 ml spirits).

• Smoking cessation: markedly reduces cardiovascular risk (although not directly BP).

• Stress reduction and relaxation techniques (e.g., meditation, biofeedback) may be helpful in some patients.

In patients with low to moderate cardiovascular risk, these measures may suffice to achieve target BP. In high-risk patients (e.g., diabetes, chronic kidney disease, prior myocardial infarction), pharmacotherapy is initiated earlier—at BP ≥130/80 mmHg.

When to Start Pharmacologic Therapy?

Indications for initiating drug therapy:

• BP ≥140/90 mmHg in individuals with low cardiovascular risk after attempts at non-pharmacological measures.

• BP ≥130/80 mmHg in high-risk patients, including:

  • Diabetes mellitus

  • Chronic kidney disease (GFR <60 ml/min)

  • Prior myocardial infarction or stroke

  • Significant left ventricular hypertrophy

Target BP values:

• <130/80 mmHg for most patients

• <140/90 mmHg for older and frail patients when lower values are not well tolerated

• <120 mmHg systolic — recommended only in U.S. guidelines for selected high-risk patients (based on SPRINT and STEP); the 2024 European guidelines do not support universal application and emphasize careful patient selection.

Pharmacotherapy of Hypertension

First-line drug classes include:

• Thiazide diuretics (e.g., chlorthalidone, indapamide)

• ACE inhibitors (e.g., lisinopril, ramipril)

• Angiotensin II receptor blockers (ARBs) (e.g., losartan, valsartan)

• Calcium channel blockers (CCBs) (e.g., lacidipine, amlodipine, diltiazem)

• Beta-blockers (e.g., bisoprolol, nebivolol)

Drug selection is based on comorbidities, age, sex, and individual tolerability. For example, in diabetics with renal impairment, ACEIs/ARBs are recommended for their nephroprotective effects.

A two-drug combination (e.g., ACEI + CCB) is often needed at the outset, especially when BP >150/100 mmHg.

Special Populations and Personalized Approach

Pregnancy requires special consideration; safe options include methyldopa, labetalol, and nifedipine, while ACEIs and ARBs are contraindicated. In older adults, begin therapy cautiously with lower doses and gradual titration. In patients with GFR <30 ml/min, thiazide diuretics are avoided due to reduced efficacy; loop diuretics are preferred when a diuretic is indicated.

Resistant Hypertension and Emergencies

Resistant hypertension is defined as BP ≥130/80 mmHg despite three antihypertensives (including a diuretic). Management includes excluding secondary causes, assessing adherence, and considering add-on therapy (e.g., spironolactone) or renal denervation.

Hypertensive crisis denotes a sudden rise in BP >180/120 mmHg with or without target-organ damage. Crises are classified as urgencies (no organ damage) and emergencies (with organ damage). Treatment involves controlled, gradual BP reduction to avoid ischemia and organ hypoperfusion.

New Therapeutic Approaches

Early and more intensive BP lowering

• Trials SPRINT, STEP, BPROAD show benefits of aggressive systolic BP lowering to <120 mmHg in high-risk patients.

• Benefits: reduced myocardial infarction, stroke, and mortality.

• Risks: hypotension, syncope, renal insufficiency.

• Not yet routinely adopted in Europe.

“Polypill” concept

• Combining multiple antihypertensives in one tablet.

• Advantages: better adherence, lower treatment cost.

• Suitable for patients with multiple comorbidities, polypharmacy, and poor adherence.

Personalized medicine

• Targeted drug selection based on pharmacogenetics, comorbidities, and phenotype.

• Example: aldosterone/renin ratio assessment in resistant hypertension.

Use of SGLT2 inhibitors

• Dapagliflozin, empagliflozin lower BP by ~3–5 mmHg independent of glycemia and provide additional cardioprotective effects.

• Particularly useful in diabetes and in patients with cardiovascular and renal disease.

Mineralocorticoid receptor antagonists (MRAs)

• Spironolactone and eplerenone are effective in resistant hypertension.

• Caution: may cause hyperkalemia and gynecomastia.

Renal denervation

• A minimally invasive intervention that reduces renal sympathetic innervation.

• Has shown favorable effects in patients with resistant hypertension.

Conclusion

Successful hypertension management requires an integrated approach encompassing patient education, regular follow-up, lifestyle modification, and optimal pharmacotherapy. Understanding modern therapeutic strategies is essential for every clinician, given the prevalence, chronic course, and serious health consequences of hypertension. Effective treatment involves more than prescribing medications: it requires thorough cardiovascular risk assessment, individualized therapy, implementation of non-pharmacological measures, and close monitoring of adherence and treatment response.

References

• 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Available at: https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Elevated-Blood-Pressure-and-Hypertension

• Li X, Zhang J, Xing Z, Liu Q, Zhou S, Xiao Y. Intensive blood pressure control for patients aged over 60: A meta-analysis of the SPRINT, STEP, and ACCORD BP randomized controlled trials. Maturitas. 2023 Jun;172:52–59. doi:10.1016/j.maturitas.2023.04.009.

• Seidu S, Willis H, Kunutsor SK, Khunti K. Intensive versus standard blood pressure control in older persons with or without diabetes: a systematic review and meta-analysis of randomised controlled trials. J R Soc Med. 2023 Apr;116(4):133–143. doi:10.1177/01410768231156997.

• Bi Y, Li M, Liu Y, Li T, Lu J, Duan P, Xu F, Dong Q, Wang A, Wang T, Zheng R, Chen Y, Xu M, Wang X, Zhang X, Niu Y, Kang Z, Lu C, Wang J, Qiu X, Wang A, Wu S, Niu J, Wang J, Zhao Z, Pan H, Yang X, Niu X, Pang S, Zhang X, Dai Y, Wan Q, Chen S, Zheng Q, Dai S, Deng J, Liu L, Wang G, Zhu H, Tang W, Liu H, Guo Z, Ning G, He J, Xu Y, Wang W; BPROAD Research Group. Intensive Blood-Pressure Control in Patients with Type 2 Diabetes. N Engl J Med. 2025 Mar 27;392(12):1155–1167. doi:10.1056/NEJMoa2412006. Epub 2024 Nov 16.