Response to The J-Point Revisited
We thank Dr Rosendorff1 for his interest in our editorial2 accompanying the article by Thune et al.3 The data presented by Thune et al3 indicated, in their words, an association (but no definite specification of cause and effect) between low blood pressure and adverse cardiovascular outcomes. As you suggest for their data, low pressure may not be an independent variable in the prediction of future adverse cardiovascular outcomes. Instead, low pressure may be the result of previous anterior myocardial infarction, Q-wave myocardial infarction, and/or degree of elevation of creatine kinase, genuine independent variables. We agree and would add that it is unclear whether low pressure contributes to adverse outcomes or is associated with other variables that contribute to it, including cessation of therapies known to reduce adverse outcomes in coronary artery disease patients (eg, angiotensin-converting enzyme inhibitors, β-receptor blockers, etc). A statistical analysis adjusted for the latter genuine independent variables would help to address this question. With regard to diastolic blood pressure, Messerli et al4 do provide rather compelling data that suggest decreased coronary perfusion resulting from excessively low pressure accounts for the increased incidence of adverse cardiovascular outcomes. In addition, in their report, the J-shaped curves did persist even after adjustment for multiple confounding variables, including age, history of myocardial infarction, heart failure, stroke, revascularization, diabetes, and cancer. The persistence of these J-shaped curves after adjustment would lend support for a cause-and-effect relationship, but again, the issue of cessation of therapies known to reduce adverse outcomes in coronary artery disease patients has not been addressed.
Additional support for a cause-and-effect relationship accompanying the J-shaped curves is provided through the Hypertension Optimal Treatment randomized trial.5 In this trial, hypertensive patients were randomly assigned on the basis of age, sex, previous antihypertensive therapy, smoking, previous myocardial infarction, previous other coronary heart disease, previous stroke, and diabetes mellitus into specific target diastolic blood pressure ranges. Results of this trial included J-shaped curves, which were most pronounced for the relationship of cardiovascular mortality and diastolic blood pressure. Importantly, the lowest reported diastolic blood pressure in the Hypertension Optimal Treatment study was 70 mm Hg, which was 10 to 20 mm Hg greater than the lowest diastolic blood pressure reported by Thune et al3 and Messerli et al.4 The Hypertension Optimal Treatment data, in conjunction with the data of Thune et al4 and Messerli et al,4 suggest that, in humans, a diastolic blood pressure <70 to 75 mm Hg may indeed contribute to decreased coronary perfusion and, consequently, increase cardiovascular mortality. As we allude to in our editorial, to definitively resolve the issue of a cause-and-effect relationship accompanying J-shaped curves relating diastolic blood pressure and adverse cardiovascular outcomes would require an appropriately powered trial (and appropriate adjustments in statistical analysis) that randomly assigns patients into different low-target diastolic blood pressure ranges. Until then, as we and Dr Rosendorff suggest, some caution might be prudent in avoiding excessively low diastolic blood pressures, and the same may be true for excessively low systolic blood pressures.
Rosendorff C. The J-curve revisited. Hypertension. 2008; 51: e34.
Denardo SJ, Anderson RD, Pepine CJ. Blood pressure targets after high risk myocardial infarction: Is it time to update the guidelines? Hypertension. 2008; 51: 26–27.
Thune JJ, Signorovitch J, Kober L, Velasquez EJ, McMurray JJV, Califf RM, Maggioni AP, Rouleau JL, Howlett J, Zelenkofske S, Pfeffer MC, Solomon SD. Effect of antecedent hypertension and follow-up blood pressure on outcomes after high-risk myocardial infarction. Hypertension. 2008; 51: 48–54.
Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. HOT Study Group. Lancet. 1998; 351: 1755–1762.