Impact of seasonal blood pressure changes on visit-to-visit blood pressure variability and related cardiovascular outcomes

Abstract

Background: Visit-to-visit blood pressure (BP) variability associates with an increased risk of cardiovascular events. We investigated the role of seasonal BP modifications on the magnitude of BP variability and its impact on cardiovascular risk.

Methods: In 25 390 patients included in the ONTARGET and TRANSCEND trials, the on-treatment systolic (S) BP values obtained by five visits during the first two years of the trials were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for BP variability quintiles (Qs), as quantified by the coefficient of variation (CV) of on-treatment mean SBP from the five visits. The relationship of BP variability with the risk of cardiovascular events and mortality was assessed by the Cox regression model.

Results: SBP was approximately 4 mmHg lower in summer than in winter regardless of confounders. Winter/summer SBP differences contributed significantly to each SBP-CV quintile. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio (HR) of the primary endpoint of the trials, i.e. morbid and fatal cardiovascular events. This association was even stronger after removal of the effect of seasonality from the calculation of SBP-CV. A similar trend was observed for secondary endpoints.

Conclusions: Winter/summer SBP differences significantly contribute to visit-to-visit BP variability. However, this contribution does not participate in the adverse prognostic significance of visit-to-visit BP variations, which seems to be more evident after removal of the BP effects of seasonality from visit-to-visit BP variations.

Graphical abstract

FIGURE 1

Monthly (January to December) systolic blood pressure (SBP) in 25 390 patients of the ONTARGET and TRANSCEND trials, separately for patients from northern European countries, southern European countries and patients from the southern hemisphere who as expected showed an inverse seasonality. Data at the bottom refer to monthly SBP means ± standard errors.

FIGURE 2

Monthly systolic BP, diastolic BP, pulse pressure and heart rate values in the patients of Fig. 1 pooled (n = 25 390). Data of patients from the southern hemisphere were corrected for inverse seasonality (see Methods). Explanations and abbreviations as in Fig. 1.

FIGURE 3

Monthly systolic blood pressure (SBP) values according to patients’ gender, age, presence or absence of type 2 diabetes mellitus, baseline SBP and mean achieved SBP during the treatment period. Data refer to patients of Figs. 1 and 2. Data from the southern hemisphere were corrected for inverse seasonality. Baseline and achieved SBP ranges are indicated in the panels. Data from different achieved SBP ranges are shown in the central and right bottom panels. Abbreviations and explanations as in preceding figures.

FIGURE 4

The upper panel shows the mean monthly SBP values in different SBP-CV quintiles, i.e. from the lowest (1) to the highest one (5). The lower panel shows the mean maximum winter and mean minimal summer SBP values according to the SBP-CV quintile 1 to 5. Data from the 25 390 patients of the preceding Figures. Abbreviations as in preceding figures.

FIGURE 5

Progressive increase in incidence of the primary end-point (Kaplan–Meier curves, cardiovascular morbidity and mortality) for each SBP-CV quintile before (conventional) and after (residual) subtraction of seasonal SBP changes. Event incidence was progressively greater from the lowest to the highest SBP-CV quintile. Quintile differences became apparent early after treatment initiation. For each quintile data were corrected for inverse seasonality and adjusted for the variables of Table 1 (see Methods). Quintiles are numbered from 1 to 5.

FIGURE 6

Progressive increase in the incidence of secondary end-points (Kaplan–Meier curves) for each SBP-CV quintile before (conventional) and after (residual) subtraction of seasonal BP changes in patients of Fig. 5. MI, myocardial infarction; HF, heart failure. Other explanations as in Fig. 5.