CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Ilke Sipahi, MD, FACC*,
E. Murat Tuzcu, MD, FACC and
Steven E. Nissen, MD, FACC
* Cleveland Clinic Foundation, Department of Cardiovascular Medicine, 9500 Euclid Avenue, Desk JJ65, Cleveland, Ohio 44195 (Email: sipahii{at}ccf.org).
Regarding our study (1), Dr. Messerli et al. state that, in patients with coronary disease, lowering diastolic blood pressure (BP) below certain levels will increase risk of acute coronary events, and they urge us to amend our conclusion, stating "the most favorable rate of progression of coronary atherosclerosis is observed in patients whose BP falls within the ‘normal’ Joint National Commission-7 category (i.e., systolic BP <120 mm Hg and diastolic BP <80 mm Hg)." They base their argument on the secondary analysis of the INVEST (International Verapamil-Trandolapril Study), which suggested a J-shaped relationship between diastolic BP and the primary outcome that included not only all-cause death and nonfatal myocardial infarction (MI), as stated in the above letter, but also nonfatal stroke (2).
However, in the INVEST study there were profound imbalances in the baseline characteristics of patients with lower and higher diastolic BP. For example, as compared to patients with a diastolic BP of 70 to 80 mm Hg, patients with diastolic BP <60 mm Hg were older (74 vs. 67 years), more likely to have a history of MI (47% vs. 32%), bypass surgery and angioplasty (48% vs. 28%), and diabetes (44% vs. 29%). More importantly, they were about 4 times more likely to have heart failure (22% vs. 5%) and cancer (11% vs. 3%). Indeed, when adjusted for these confounders, the J-shaped relationship between diastolic BP and the primary outcome disappeared. This shows that the increased primary outcome with lower diastolic BP levels was due to the fact that these patients were sicker beforehand (i.e., reverse causality). In fact, analysis of MRFIT (Multiple Risk Factor Intervention Trial) data involving more than 300,000 men with a median follow-up of 22 years showed that, within the normal BP category of <120/80 mm Hg, there exists no relationship between diastolic BP and cardiovascular disease mortality (3). Our conclusion about the importance of having normal BP levels to slow progression or induce regression of coronary atherosclerosis as assessed by intravascular ultrasound is also supported by other epidemiological data including the Framingham study, which showed that incidence of MI is lowest in patients with normal BP, intermediate in those with prehypertension, and highest in those with hypertension (4).
We thank Dr. Messerli et al. for their interest in our study.
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References
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- Sipahi I, Tuzcu EM, Schoenhagen P, et al. Effects of normal, pre-hypertensive, and hypertensive blood pressure levels on progression of coronary atherosclerosis J Am Coll Cardiol 2006;48:833-838.[Abstract/Free Full Text]
- Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006;144:884-893.[Abstract/Free Full Text]
- Domanski M, Mitchell G, Pfeffer M, et al. Pulse pressure and cardiovascular disease-related mortality: follow-up study of the Multiple Risk Factor Intervention Trial (MRFIT) JAMA 2002;287:2677-2683.[Abstract/Free Full Text]
- Qureshi AI, Suri MF, Kirmani JF, Divani AA, Mohammad Y. Is prehypertension a risk factor for cardiovascular diseases? Stroke 2005;36:1859-1863.[Abstract/Free Full Text]
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