Author + information
- Paolo Palatini, MD∗ ()
- ↵∗Medicina Vascolare, Dipartimento di Medicina, University of Padova, via Giustiniani, 2, 35128 Padova, Italy
I read with great interest the paper by Messerli et al. (1) on the effects of heart rate (HR) reduction in hypertension (1). The authors affirm that HR lowering in hypertension has been documented to progressively increase cardiovascular mortality. This statement was mainly based on a meta-analysis of 9 clinical trials encompassing more than 60,000 hypertensive patients (2). I suggest caution is needed when interpreting these findings for several reasons, but particularly for the possible fallacy of meta-analyses based on aggregate data. Using averages or proportions of patient data often leads to misinterpretation of the effect of patient characteristics on outcomes. Indeed, the analyses of individual patient data made in the 3 main trials included in Bangalore et al. meta-analysis (encompassing more than 80% of the patients) led to opposite results (3). In the INternational VErapamil-SR/trandolapril Study, post-treatment lower HR was associated with a reduced risk of adverse outcome. In the Losartan Intervention For Endpoint reduction study, an HR of persistently <84 beats/min during the follow-up was associated with a much lower risk of cardiovascular and all-cause mortality. In the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm study, a lower follow-up HR was associated with reduced cardiovascular mortality. In all trials, the post-treatment HR was a better predictor of cardiovascular events than baseline HR. These results are clearly in contrast with those extrapolated from aggregate data (1). The explanation about the claimed detrimental effects of HR lowering in hypertension is also questionable. There is no doubt that a lower HR implies a greater augmentation index, but this cannot be translated “tout court” into increased arterial stiffness because the augmentation index is modulated by many other variables. Acute studies have shown that pulse wave velocity, a well-accepted index of arterial stiffness, actually increases with increasing HR (0.3 m/s/10 beats/min) (4) and increased HR was a powerful predictor of accelerated progression of arterial stiffness in the long term. The claimed “profibrotic effect” of beta-blockers on the arterial wall, which would result in increased arterial stiffness (1), is thus unlikely to occur. Indeed, a pooled analysis of 4 major intravascular ultrasound trials (5) demonstrated that beta-blocker treatment was associated with a statistically significant reduction in the yearly progression rate of coronary atherosclerosis (atheroma reduction, 2.4 mm3/year). For these reasons, this author believes that the relationship between pharmacological HR lowering and outcome in hypertension is far from being established and that only a clinical trial can clarify this controversial issue.
Please note: Dr. Palatini has had advisory relationships with Merck Serono.
Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper. George Bakris, MD, served as Guest Editor for this paper.
- American College of Cardiology Foundation
- Messerli F.H.,
- Rimoldi S.F.,
- Bangalore S.,
- et al.
- Bangalore S.,
- Sawhney S.,
- Messerli F.H.