Journal of the American College of Cardiology
ReplyPulse Pressure and Cardiovascular Death
Author + information
- Senthil Selvaraj, MD, MA,
- P. Gabriel Steg, MD,
- Yedid Elbez, MSc,
- Emmanuel Sorbets, MD,
- Laurent J. Feldman, MD,
- Kim A. Eagle, MD,
- E. Magnus Ohman, MD,
- Jacques Blacher, MD, PhD and
- Deepak L. Bhatt, MD, MPH∗ (dlbhattmd{at}post.harvard.edu)
- ↵∗Heart and Vascular Center, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115
We appreciate the thoughtful comments of Dr. Aznaouridis and colleagues on our paper studying the relationship between brachial pulse pressure (PP) and adverse cardiovascular outcomes in the REACH (REduction of Atherothrombosis for Continued Health) registry (1). As Dr. Aznaouridis and colleagues point out, the J-shaped relationship between PP and cardiovascular death may not be fully explained by confounding from unmeasured aortic stenosis. A few explanations may account for this finding. First, many REACH participants were prescribed blood pressure (BP) medications for secondary prevention, and the sickest patients may have been maintained on their BP medications to achieve ancillary benefits (anti-ischemic or anti-remodeling effects) while yielding a lower PP. Second, heart rate, a potentially confounding variable, was not collected in the REACH database (2). Third, the associations between low BP and PP with higher event rates are derived largely from observational studies; thus, low PP may reflect “reverse causality” and mark frail or sicker patients, as hypothesized in published reports on systolic and diastolic BP (3). The results of the randomized SPRINT (Systolic Blood Pressure Intervention Trial) study support this hypothesis, wherein frequent standing BP measurements were performed and treatment was decreased in cases of orthostatic hypotension, thus explaining the low rate of related adverse events (4). Therefore, the participants with lower systolic BP (and PP) on treatment were necessarily healthier, given their ability to tolerate higher-dose treatment.
We share concerns similar to those of Dr. Aznaouridis and colleagues regarding the feasibility of measuring central PP in large-scale analyses. In addition, the prognostic value of central hemodynamic measurements over peripheral measurements has not been established, given several conflicting studies, partly driven by underpowered analyses as well as high correlation between the two methods (2). Therefore, the additional benefit of central PP may exist for a select subgroup of patients, and identifying this subgroup is of clinical interest. Ambulatory BP monitoring also improves risk stratification, and whether it provides significant benefit in lieu of central BP measurements has been studied with promising results (5), but it needs larger confirmatory studies. Such important questions with broad implications, however, merit further adequately powered research investigations on the ideal risk stratification methods using central versus peripheral BP measurements.
Footnotes
Please note: Dr. Steg has received research grants from Sanofi and Servier awarded to INSERM U-698 and the New York University School of Medicine; serves as a consultant or receives speaker’s fees from Ablynx, Amarin, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Lilly, Medtronic, Merck Sharp & Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, Servier, and the Medicines Company; and holds stock in Aterovax. Dr. Feldman has received research grants from Sanofi and Bristol-Myers Squibb. Dr. Blacher has received a research grant from Servier; and speaker’s fees from AstraZeneca, Bayer, BMS, Bouchara Recordati, Daïchii-Sankyo, GSK, Ipsen, Menarini, Merck Serono, MSD, Novartis, Pileje, Roche, Sanofi, Servier, and Takeda. Dr. Bhatt is on the advisory board of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; and on the Board of Directors of Boston VA Research Institute and the Society of Cardiovascular Patient Care; is the chair of the American Heart Association Get With the Guidelines Steering Committee; is on data monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, acc.org), Belvoir Publications (editor-in-chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor-in-chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (associate editor; section editor, Pharmacology), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), WebMD (CME steering committees); is the deputy editor of Clinical Cardiology; has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
