Increased Intervisit Blood Pressure Variability and β-Blockade: Measurement Imprecision Related to Bradycardia?
To the Editor:
In their editorial commentary, Dolan and O'Brien1 reviewed and provided clinical perspective to the series of articles last March in which Rothwell and colleagues2,3 established a clear link between long-term blood pressure variability and hypertension-related outcome. The conceptual introduction of intervisit variability in blood pressure consolidated previous findings based on intra-arterial and noninvasive 24-hour ambulatory measurements.4 Additional observations will help shape the ripening assimilation to management guidelines. In this regard, Webb et al,3 as well as Rothwell et al2 have suggested a medication-class effect on blood pressure variability, which might mediate outcome differences. As highlighted in the editorial,1 assignment to β-adrenergic blockade–based treatment was associated with increased intervisit variability and worse outcome.2 Although a direct effect of a drug on cardiovascular reactivity is plausible, it is somewhat in contrary to the strong link between the mean blood pressure and its variance.5 We suggest an alternative explanation for the association of β-blockers with intervisit variability. Determination of blood pressure relies on detection of Korotkoff sounds (by auscultation) or the pulse wave oscillations (by oscillatory devices). Bradycardia can decrease the precision of these determinations; namely, it can increase the scatter around the true level of blood pressure, because the observer (listener or device) is awaiting the next Korotkoff sound or pulse wave, while deflating the cuff at constant rate. Indeed, in our ambulatory blood pressure measurement data set of referred patients,5 we found a connection between increased awake blood pressure variability and slow heart rate, both measured by the automated ambulatory blood pressure measurement device (Figure). Thus, we speculate that bradycardia induced by β-blockers mediates lack of diagnostic precision, which might have impact on outcome rather than true increase in blood pressure variability. The differential effects of angiotensin antagonists and calcium channel blockers on heart rate might follow the same rationale. In future studies, it would be interesting to explore the degree to which drug effects on variability withstand adjustment for heart rate.
Dolan E, O'Brien E. Blood pressure variability: clarity for clinical practice. Hypertension. 2010; 56: 179–181.
Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlöf B, Poulter NR, Sever PS, for the ASCOT-BPLA and MRC Trial Investigators. Effects of β-blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol. 2010; 9: 469–480.
Mancia G, Bombelli M, Facchetti R, Mancia G, Bombelli M, Facchetti R. Long-term prognostic value of blood pressure variability in the general population: results of the Pressioni Arteriose Monitorate e Loro Associazioni Study. Hypertension. 2007; 49: 1265–1270.