Evidence for the influence of ambulatory blood pressure on prognosis derives mainly from population-based studies and a few relatively small clinical investigations. This study examined the associations of blood pressure measured in the clinic (clinic blood pressure) and 24-hour ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of patients in primary care.
We analyzed data from a registry-based, multicenter, national cohort that included 63,910 adults recruited from 2004 through 2014 in Spain. Clinic and 24-hour ambulatory blood-pressure data were examined in the following categories: sustained hypertension (elevated clinic and elevated 24-hour ambulatory blood pressure), “white-coat” hypertension (elevated clinic and normal 24-hour ambulatory blood pressure), masked hypertension (normal clinic and elevated 24-hour ambulatory blood pressure), and normotension (normal clinic and normal 24-hour ambulatory blood pressure). Analyses were conducted with Cox regression models, adjusted for clinic and 24-hour ambulatory blood pressures and for confounders.
During a median follow-up of 4.7 years, 3808 patients died from any cause, and 1295 of these patients died from cardiovascular causes. In a model that included both 24-hour and clinic measurements, 24-hour systolic pressure was more strongly associated with all-cause mortality (hazard ratio, 1.58 per 1-SD increase in pressure; 95% confidence interval [CI], 1.56 to 1.60, after adjustment for clinic blood pressure) than the clinic systolic pressure (hazard ratio, 1.02; 95% CI, 1.00 to 1.04, after adjustment for 24-hour blood pressure). Corresponding hazard ratios per 1-SD increase in pressure were 1.55 (95% CI, 1.53 to 1.57, after adjustment for clinic and daytime blood pressures) for nighttime ambulatory systolic pressure and 1.54 (95% CI, 1.52 to 1.56, after adjustment for clinic and nighttime blood pressures) for daytime ambulatory systolic pressure. These relationships were consistent across subgroups of age, sex, and status with respect to obesity, diabetes, cardiovascular disease, and antihypertensive treatment. Masked hypertension was more strongly associated with all-cause mortality (hazard ratio, 2.83; 95% CI, 2.12 to 3.79) than sustained hypertension (hazard ratio, 1.80; 95% CI, 1.41 to 2.31) or white-coat hypertension (hazard ratio, 1.79; 95% CI, 1.38 to 2.32). Results for cardiovascular mortality were similar to those for all-cause mortality.
Ambulatory blood-pressure measurements were a stronger predictor of all-cause and cardiovascular mortality than clinic blood-pressure measurements. White-coat hypertension was not benign, and masked hypertension was associated with a greater risk of death than sustained hypertension. (Funded by the Spanish Society of Hypertension and others.)
Supported by the Spanish Society of Hypertension and by an unrestricted grant from Lacer Laboratories, Spain. Specific funding for this analysis was obtained from a grant (PI16/01460) from Fondo de Investigaciones Sanitarias of Instituto de Salud Carlos III (cofunded by Fondo Europeo de Desarrollo Regional and Fondo Social Europeo) and from Centro de Investigación Biomédica en Red of Epidemiology and Public Health, Spain. Dr. Williams is a Senior Investigator for the National Institute for Health Research, and his research is supported by the University College London Hospitals Biomedical Research Centre.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Dr. de la Sierra reports receiving lecture fees from Abbott, Daiichi Sankyo, Menarini, and Lacer, and receiving advisory board fees and lecture fees from Pfizer; Dr. Segura, receiving lecture fees from AstraZeneca, Chiesi, Daiichi Sankyo, Medtronic, Pfizer, Menarini, Esteve, and Servier; and Dr. Williams, receiving consulting fees from Vascular Dynamics, Relypsa, and Novartis, honoraria from Daiichi Sankyo, Boehringer Ingelheim, Servier, and Pfizer, and serving as an advisor to HealthStats PTE, Singapore. No other potential conflict of interest relevant to this article was reported.
We thank all the investigators of the Spanish Ambulatory Blood Pressure Registry and the Spanish National Institute of Statistics for the development and continuous improvement in quality of vital-statistics data offered to researchers.