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Seasonal Blood Pressure Variation: A Neglected Confounder in Clinical Hypertension Research and Practice

1Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, School of Medicine, Third Department of Medicine, Sotiria Hospital, Athens, Greece; 2Studium Patavinum, Department of Medicine, University of Padova, Padua, Italy; 3University of Toronto, Consultant Cardiologist, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; 4The Conway Institute, University College Dublin, Dublin, Ireland; 5Department of Medicine and Surgery, University of MilanoBicocca, Milano, Italy; 6Istituto Auxologico Italiano, IRCCS, Cardiology Unit and Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital, Milano, Italy; 7Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.


Seasonal Blood Pressure Variation: A Neglected Confounder in Clinical Hypertension Research and Practice
George S. Stergiou, 1 Paolo Palatini, 2 Anastasios Kollias, 1 Konstantinos G. Kyriakoulis, 1 Martin Myers, 3 Eoin O'Brien, 4 Gianfranco Parati, 5,6 and Pietro Amedeo Modesti 7 For more than a century blood pressure (BP) measured by the doctor in the office has been recognized as an indisputable predictor of cardiovascular morbidity and mortality. 1,2 However, BP is known to show dynamic variability in response to the physical and emotional challenges of routine daily activities, which may confound any investigation involving BP changes. 3 Many factors are known to influence BP readings, 1 including the physical and emotional challenges of routine daily activities, the setting (office, home, work), the observer (doctor, nurse, self-measurement, automated unattended), the device (auscultatory, automated), the patient's posture (seated, standing, lying), the time of measurement (morning, evening, nighttime sleep), the measurement schedule (number of readings and those averaged), talking, exercise, meals, smoking, coffee, alcohol, and time of antihypertensive drug intake. In recognizing these confounding factors, international recommendations have standardized the methodologies for BP evaluation in the office and out-of-the-office to minimize their influence and improve the accuracy of BP evaluation. 4,5 In the American Journal of Hypertension Gepts et al. 6 have added to this list of confounders by demonstrating how seasonal variations in BP can influence the interpretation of interventions aiming at improving BP control. In this study, when seasonality was not accounted for, a significant negative association of the study intervention on BP control was observed. However, when BP seasonality was taken into account, they showed that the intervention had no effect on BP control.
It is surprising that this major confounder has been systematically ignored for so long. A recent review and metaanalysis of 47 published trials which examined seasonal changes in BP 7 showed that the seasonal BP variation is a global phenomenon affecting all age groups, both sexes, and normotensive and hypertensive subjects. Meta-analysis of these trials showed an average seasonal BP decline in the high-temperature season of 6/3 mm Hg (systolic/diastolic) for office and home BP and 3.5/2 mm Hg for daytime ambulatory BP, and a small rise in nighttime ambulatory BP (1.3/0.5 mm Hg). 7 Importantly, these changes were greater in treated hypertensive patients and in older individuals. 7 Thus, these findings suggest that the magnitude of the seasonal BP change is comparable to the reduction that might be expected from an effective antihypertensive drug, particularly in elderly patients.
The 2017 American College of Cardiology/American Heart Association 2 as well as the 2018 European Society of Cardiology/European Society of Hypertension guidelines 1 for hypertension do not mention the seasonal BP variation phenomenon, and no recommendations are provided for guiding the practicing physicians on its potential implications in treating hypertension.  8 in which the evidence on the epidemiology, pathophysiology, relevance, and magnitude of the seasonal BP variation was presented together with recommendations for practicing physicians. 8 The potential impact of the seasonal BP variation on the interpretation of clinical hypertension research was also discussed, 8 leading to the conclusion that failure to take this factor into account may have distorted the findings of numerous published clinical hypertension trials and epidemiological surveys (Table 1).
In conclusion, the article by Gepts et al. 6 clearly demonstrated that the environmental temperature must be taken into account in clinical hypertension research when evaluating or comparing BP measurements taken on different occasions throughout different seasons. Clinical trials using office or out-of-office BP measurements as efficacy measures, which last long enough to be influenced by ambient temperature change, need to be adjusted for the seasonal variation in BP. Such an adjustment should be proportional to the change in environmental temperature and should be based on BP changes observed at the same time interval without intervention and assessed using the same BP measurement methodology.

DISCLOSURE
The authors declared no conflict of interest.