Abstract
Background: Hypertension is the leading modifiable risk factor for cardiovascular, cerebrovascular, and kidney disease. In Mexico, 29.1% of adults have hypertension, while only 60.1% of pharmacologically treated individuals achieve blood-pressure control. Difficult-to-control hypertension and true resistant hypertension (RH) represent high-risk phenotypes associated with greater cardiovascular, renal, and healthcare burden.Methods: A prevalence-based cost-of-illness model was developed from the Mexican healthcare-system perspective, with a secondary societal perspective. ENSANUT 2021–2024 data were combined with international estimates of apparent treatment-resistant hypertension (aTRH) and true resistant hypertension (RH). Direct hospitalization costs were estimated using official 2026 Instituto Mexicano del Seguro Social (IMSS) unit costs. For long-term projections, the aggregate planning model was strengthened by indexing the exposed adult population to annual CONAPO demographic projections, explicitly considering all-cause mortality as a competing risk and cardiovascular mortality as a component of that mortality burden. To estimate costs attributable specifically to RH, a counterfactual non-resistant-hypertension risk was derived from adjusted comparative hazard ratios, and only the excess event risk above that baseline was assigned to RH.Results: Approximately 24.4 million adults have hypertension, 12.5 million receive pharmacological treatment, and 5.0 million remain uncontrolled in the original epidemiological cascade. An estimated 1.84 million have aTRH and 1.29 million have true RH. The total modeled hospitalization burden occurring among patients with true RH is approximately MXN $5.62 billion annually. After subtracting the counterfactual hospitalization burden expected in otherwise comparable patients with non-resistant hypertension, the incremental hospitalization cost attributable specifically to RH is approximately MXN $1.08 billion per year (MXN$835 per patient-year). Under 2%, 3%, and 4% annual sensitivity growth in event intensity/resource use, the corresponding 20-year cumulative RH-attributable direct-cost envelope is approximately MXN $26.2, $28.9, and $32.1 billion, respectively, before discounting.Conclusion: Difficult-to-control and resistant hypertension represent a substantial clinical and economic burden in Mexico. Distinguishing the total hospitalization burden observed among patients with RH from the incremental burden attributable to treatment resistance materially reduces the risk of overestimation. Long-term estimates remain planning scenarios and should be interpreted in conjunction with demographic change, mortality, competing risks, and uncertainty in Mexican RH-specific event rates. These findings support systematic detection, out-of-office confirmation, optimized combination therapy, and development of a prospective national RH registry.