By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, David Geffen School of Medicine at UCLA
Dr. Karpman reports no financial relationships relevant to this field of study.
SYNOPSIS: In patients suffering from hypertension and coronary artery disease in routine clinical practice, systolic blood pressure of < 120 mmHg and diastolic blood pressure < 70 mmHg each were associated with adverse cardiovascular outcomes, including mortality, supporting the existence of a J-curve phenomenon.
SOURCE: Vidal-Petiot E, Ford I, Greenlaw N, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: An international cohort study. Lancet 2016 388:2142-2152.
Lowering blood pressure (BP) in patients suffering from hypertension reduces the risk of cardiovascular events and death,1,2 but the optimum target BP remains unresolved.1-4 Some randomized trials have not shown a benefit of BP targets of < 140/90 mmHg. In fact, some published analyses have suggested that the benefits of BP lowering even may be reversed below a certain threshold,5-9 the so-called J-curve phenomenon.6 Vidal-Petiot et al studied the association between achieved BP levels and cardiovascular outcomes in a large cohort of patients presenting with stable coronary artery disease treated for hypertension in the CLARIFY study.11
The CLARIFY study was a prospective observational, longitudinal registry of patients presenting with stable coronary artery disease and included 32,703 patients receiving standard care for hypertension. The study was conducted in 45 countries, excluding the United States. All eligible patients presented with stable coronary artery disease and were receiving treatment with at least one antihypertensive drug for hypertension, defined as BP readings > 140/90 mmHg. BP in the office was measured annually in patients after a rest of five minutes in the sitting position. The primary outcomes measured were the composite of cardiovascular death, myocardial infarction, or stroke, and the measured secondary outcomes were each component of the primary endpoints and all-cause death and hospital admission for heart failure. The results of this very large observational, international cohort study revealed that elevated systolic BP and/or low diastolic BP levels were associated with an increased risk of cardiovascular events in patients suffering from coronary artery disease and hypertension. The authors observed the increased risk both over a threshold of 140/90 mmHg and under a threshold of 120/70 mmHg, resulting in a J-curve phenomenon.
The results from the CLARIFY trial are consistent with the results from previous analyses conducted in other randomized trials that studied patients with hypertension and coronary artery disease.7,12 Although the J-curve effect was robust and persisted after multiple adjustment procedures for potential confounders, the study was based on a large cohort from routine clinical practices with no predefined BP intervention, which might confound the analysis.
Of course, the strength of the study lies in the accuracy of the baseline and follow-up BP determinations. Another particular strength of the study is that it included a large international cohort of patients treated under real-life conditions, which might provide greater validity than the highly selected populations studied in numerous published randomized trials.13
The benefit of the observations is that they are in agreement with the results of other published studies, which concluded that the benefit of lowering BP to < 140 mmHg remains unquestionable, whereas the benefit of lowering BP to < 130 mmHg is uncertain.6,7
Systolic BP > 140 mmHg should be lowered to at least 130 mmHg, but lowering systolic BP to less than that value may actually cause harm. Lowering diastolic BP to 70-79 mmHg is associated with a better outcome than leaving diastolic BP at ≥ 80 mmHg, which is consistent with results from SPRINT.14 However, trial results stand as strong evidence against lowering diastolic BP to < 70 mmHg.
Clinicians should be fully aware of the fact that both systolic and diastolic BP readings should be carefully managed and, if abnormal, be brought to appropriate levels as outlined above, but not to abnormally low or high levels.
- Zanchetti A, Thomopoulos C, Parati G. Randomized controlled trials of blood pressure lowering in hypertension: A critical reappraisal. Circ Res 2015;116:1058-1073.
- Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: A systematic review and meta-analysis. Lancet 2016;387:957-967.
- Kjeldsen SE, Lund-Johansen P, Nilsson PM, Mancia G. Unattended blood pressure measurements in the systolic blood pressure intervention trial: Implications for entry and achieved blood pressure values compared with other trials. Hypertension 2016;67:808-812.
- Jones DW, Weatherly L, Hall JE. SPRINT: What remains unanswered and where do we go from here? Hypertension 2016;67:261-262.
- Mancia G, Grassi G. Aggressive blood pressure lowering is dangerous: The J-curve: Pro side of the argument. Hypertension 2014;63:29-36.
- Cruickshank JM, Thorp JM, Zacharias FJ. Benefits and potential harm of lowering high blood pressure. Lancet 1987;1:581-584.
- 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.
- Bangalore S, Messerli FH, Wun CC, et al. J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Eur Heart J 2010;31:2897-2908.
- Mancia G, Schumacher H, Redon J, et al. Blood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan Alone and In combination with Ramipril Global Endpoint Trial (ONTARGET). Circulation 2011;124:1727-1736.
- Sim JJ, Shi J, Kovesdy CP, et al. Impact of achieved blood pressures on mortality risk and end-stage renal disease among a large, diverse hypertension population. J Am Coll Cardiol 2014;64:588-597.
- Vidal-Petiot E, Ford I, Greenlaw N, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: An international cohort study. Lancet 2016 388:2142-2152.
- Messerli FH, Panjrath GS. The J-curve between blood pressure and coronary artery disease or essential hypertension: Exactly how essential? J Am Coll Cardiol 2009;54:1827-1834.
- Rothwell PM. External validity of randomized controlled trials: “To whom do the results of this trial apply?” Lancet 2005;365:82-93.
- SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood pressure control. N Engl J Med 2015;373:2103-2116.