Abstract Body (Do not enter title and authors here): Background: Resistant hypertension is characterized by the persistence of elevated office or clinic blood pressure despite the use of three antihypertensive agents. Ambulatory blood pressure monitoring helps to distinguish between true (24-hour blood pressure ≥ 130 or ≥ 80 mmHg) and white-coat (24-hour blood pressure < 130/80 mmHg) resistant hypertension. The aim of the study was to evaluate the risk of all-cause and cardiovascular mortality in resistant hypertension as compared to controlled hypertension, as well as in true versus white-coat resistant hypertension.

Methods: From the Spanish Ambulatory Blood Pressure Registry, we selected 8146 patients with controlled hypertension (office blood pressure < 140/90 mmHg while on treatment with three or less antihypertensive drugs), and 8577 with resistant hypertension (office blood pressure ≥ 140 or ≥ 90 mmHg while on treatment with 3 or more antihypertensive drugs). All-cause and cardiovascular mortality (median follow-up 9.7 years) were compared between both groups as well as between patients with white-coat (3289) and true (5288) resistant hypertension. Hazard ratios from Cox models unadjusted and after adjustment for clinical confounders were used for such comparisons.

Results: Compared to controlled hypertension, resistant hypertension was associated with an increased risk in all-cause mortality (hazard ratio [HR]: 1.21; 95% CI: 1.12-1.30) and cardiovascular mortality (1.33; 1.17-1.51) in confounder-adjusted models. Compared to white-coat resistant hypertension, true resistant hypertension was also associated with an increased risk of all-cause (1.45; 1.32-1.60) and cardiovascular (1.68; 1.43-1.98) mortality. When true and white-coat resistant hypertension were separately compared with controlled hypertension, true, but not white-coat resistant hypertension was associated with an increased risk of all-cause and cardiovascular mortality.

Conclusion: Resistant hypertension is associated with an increased risk of all-cause and cardiovascular mortality with respect to controlled hypertension. Moreover, 24-h blood pressure is a powerful determinant of risk in resistant hypertension.