BACKGROUND: Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan. METHODS: In 4,663 young (18-49 years) and 7,185 older adults (≥50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints. RESULTS: In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were ≤2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P ≤ 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3. CONCLUSIONS: From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.

1st Department of Cardiology Interventional Electrocardiology and Hypertension Jagiellonian University Medical College Kraków Poland

Alzheimer's Disease Resource Center for Minority Aging Research University of Texas Rio Grande Valley Brownsville Texas USA

Asociación Española Primera de Socorros Mutuos Montevideo Uruguay

Biomedical Science Group Faculty of Medicine University of Leuven Leuven Belgium

Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluation Shanghai Institute of Hypertension Shanghai Key Laboratory of Hypertension Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai China

Centre for Molecular and Vascular Biology KU Leuven Department of Cardiovascular Sciences University of Leuven Leuven Belgium

Centro de Nefrología and Departamento de Fisiopatología Hospital de Clínicas Universidad de la República Montevideo Uruguay

Conway Institute University College Dublin Dublin Ireland

Department of Cardiology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Department of Human Genetics University of Texas Rio Grande Valley School of Medicine Brownsville Texas USA

Department of Hygiene and Public Health Teikyo University School of Medicine Tokyo Japan

Department of Hypertension Medical University of Gdańsk Gdańsk Poland

Department of Medicine University of Padova Padova Italy

Department of Neurosciences University of Texas Rio Grande Valley School of Medicine Brownsville Texas USA

Division of Cardiology Department of Internal Medicine University Hospitals Leuven Leuven Belgium

Faculty of Medicine Charles University Pilsen Czech Republic

Faculty of Medicine Hebrew University Department of Internal Medicine Hadassah Hebrew University Medical Center Jerusalem Israel

Institute of Internal and Preventive Medicine Internal and Preventive Medicine Branch of the Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Science Novosibirsk Russian Federation

Laboratory of Neurosciences Faculty of Medicine University of Zulia Maracaibo Zulia Venezuela

Research Institute Alliance for the Promotion of Preventive Medicine Mechelen Belgium

Research Unit Hypertension and Cardiovascular Epidemiology KU Leuven Department of Cardiovascular Sciences University of Leuven Leuven Belgium

Section of Geriatrics Department of Public Health and Caring Sciences Uppsala University Uppsala Sweden

Steno Diabetes Center Copenhagen Gentofte and Center for Clinical Research and Prevention Bispebjerg and Frederiksberg Hospital Frederiksberg Denmark

Stroke and Hypertension Unit Blanchardstown Dublin Ireland

Tohoku Institute for Management of Blood Pressure Sendai Japan

Yazmonit Ltd Jerusalem Israel

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