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It is well established that lowering blood pressure (BP) in patients with hypertension is associated with cardiovascular protection. Therefore, BP goals have been defined by international hypertension guidelines (<140/90 mmHg; <130/80 mmHg for patients with type 2 diabetes). However, the relationship of BP with prognosis is complex, and controlling office BP may not be enough to optimally manage total cardiovascular risk. It is becoming clear that out-of-office BP measurements have important prognostic value. In the observational Pressioni Arteriose Monitorate E Loro Associazioni study, the risk of cardiovascular death over 11 years was progressively higher with 10-mmHg increases in office, home, or ambulatory BPs. Smooth control of 24-h BP may be of even greater importance, as the early morning BP surge, nighttime BP, and BP variability are associated with significant risk. A further consideration in managing total cardiovascular risk is the need for multiple antihypertensive agents to control BP.