Journal of Human Hypertension (2016) 30, 293–294 © 2016 Macmillan Publishers Limited All rights reserved 0950-9240/16 www.nature.com/jhh
COMMENTARY
Pulse pressure and cardiovascular risk in diseased patients P Jankowski1 and T Weber2 Journal of Human Hypertension (2016) 30, 293–294; doi:10.1038/ jhh.2015.83; published online 13 August 2015
High blood pressure (BP) is considered a major cardiovascular risk factor. Data from observational studies involving more than 1 million individuals without pre-existing vascular disease have indicated that coronary and cerebrovascular mortality increases progressively with increasing systolic and diastolic brachial BP.1 This relation not necessarily is the same in ‘diseased’ subjects. In patients with coronary artery disease, the relation may be J- or U-shaped, with higher event rates at very low and very high blood pressures.2,3 In addition, brachial pulse pressure (PP), the difference between systolic and diastolic BP, is a major cardiovascular risk factor directly related to cardiovascular events.4 However, these findings are not without exception. Several studies in patients with systolic heart failure showed an inverse relationship between PP and the cardiovascular risk.5,6 In addition, in the study published in the present issue of the Journal of Human Hypertension, Theilade et al.7 failed to show an independent relationship between brachial PP and cardiovascular events in a high-risk population with diabetes, chronic kidney disease and anemia. Importantly, systolic and diastolic BP were not related to cardiovascular risk in this highly selected population as well. These results may suggest that BP in general and PP in particular is useless in risk stratification in patients with diabetes, chronic kidney disease and anemia. Several potential pathophysiological mechanisms are appropriately discussed by the authors to explain the existence of the above discrepancies. The first explanation could be an epiphenomenon of chronic illness, which increases noncardiovascular mortality. Second, medical treatment may alter the relationship between BP components and cardiovascular risk. Indeed, study participants were adequately treated with a high proportion receiving renin–angiotensin–aldosteron system blockers, and median BP was 136/71 mm Hg. In addition, it is reasonable to suspect that BP-lowering treatment was modified during the observational period. Probably, this occurred more often in subjects with high BP leading to a blunted prognostic value of the baseline BP. Third, brachial PP is only a crude estimate of arterial stiffening, inferior to direct measures of central hemodynamics and aortic stiffness.8 Fourth, following the same lines of argument, the central-to-brachial pressure wave amplification should be taken into account. There is increasing evidence that the difference between central and peripheral BP impacts the predictive value of brachial BP. Although the difference between central and peripheral BP is smaller in older subjects9 as well as in those with diseases leading to reduced arterial wall compliance (for example, renal insufficiency, diabetes), the difference still may have clinical significance. The last and most likely explanation is the relationship between left ventricular (LV) systolic function and PP. In contrast to normal systolic function, where measures of
Table 1. The risk of primary end point (cardiovascular death or nonfatal myocardial infarction or nonfatal stroke or nonfatal cardiac arrest or myocardial revascularization or heart transplantation) in the Aortic Blood Pressure and Survival Study population according to the left ventricular ejection fraction14 Univariate analysis
EF ⩽ 50% EF 450%
0.98 (0.87–1.11) 1.13 (1.04–1.23)
Multivariate analysis Model 1
Model 2
1.08 (0.94–1.24) 1.14 (1.03–1.26)
1.16 (1.01–1.34) 1.14 (1.03–1.26)
Model 1 contains typically used variables: age, sex, diabetes, creatinine level, treatment (percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)), and history of smoking and myocardial infarction. Model 2 contains the same variables as in Model 1 plus left ventricular ejection fraction. Hazard ratios (95% confidence intervals) are presented according to 10 mm Hg increase in ascending aortic pulse pressure.
pulsatile function (PP, wave reflection parameters) are related to aortic and arterial elastic properties, when systolic function is severly impaired, the left ventricle cannot cope with pulsatile afterload, ejection ceases early, and PP and wave reflection parameters decline. The net result is an inverse relationship between ejection fraction (and other measures of LV function) and pulsatile hemodynamics.10–12 Supporting this concept, pulse wave velocity, a direct measure of aortic stiffness, was directly related to cardiovascular mortality in patients with severly impaired systolic function, but PP showed an inverse relationship.13 Table 1 presents hazard ratios related to PP measured in the ascending aorta in coronary patients (the subanalysis of the data from the Aortic Blood Pressure and Survival Study14). It could be concluded that PP is not related to the prognosis in patients with impaired systolic function, if LV ejection fraction is not included in the multivariate model. However, inclusion of the latter variable changes the results (and the conclusion). Unfortunately, Theilade et al. could not include LV systolic function in their statistical analysis. Although LV function in the study is unknown, one-third of the participants had a history of heart failure, and one-third had coronary artery disease, substantiating the suspicion that a reasonable proportion of the study participants had impaired systolic function. It should be underlined that although brachial PP seems to be a rather weak measure of cardiovascular risk in severely diseased patients (for example, subjects with diabetes and chronic kidney disease or severe systolic heart failure), the present results of Theilade et al. do not necessarily deny its involvement in the pathogenesis of major cardiovascular events in these populations. Nowadays, there is no doubt about the presence of significant relation between the pulsatile BP component and atherosclerosis and its complications.15 Theilade et al. should be congratulated for
1 First Department of Cardiology and Hypertension, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland and 2Cardiology Department, Klinikum WelsGrieskirchen, Wels, Austria. Correspondence: Professor P Jankowski, First Department of Cardiology and Hypertension, Jagiellonian University Medical College, 17 Kopernik St., 31-501 Kraków, Poland. E-mail:
[email protected]
Commentary
294 their analysis, but their results should be also seen as a call for including measures of LV systolic function in analyses of pulsatile hemodynamics and cardiovascular risk. CONFLICT OF INTEREST The authors declare no conflict of interest.
REFERENCES 1 Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–1913. 2 Bangalore S, Messerli FH, Wun CC, Zuckerman AL, DeMicco D, Kostis JB 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. 3 Denardo SJ, Messerli FH, Gaxiola E, Aranda JM Jr, Cooper-Dehoff RM, Handberg EM et al. Coronary revascularization strategy and outcomes according to blood pressure (from the International Verapamil SR-Trandolapril Study [INVEST]). Am J Cardiol 2010; 106: 498–503. 4 Zhao L, Song Y, Dong P, Li Z, Yang X, Wang S. Brachial pulse pressure and cardiovascular or all-cause mortality in the general population: a meta-analysis of prospective observational studies. J Clin Hypertens (Greenwich) 2014; 16: 678–685. 5 Schillaci G, Di Luzio S, Coluccini M, Gonzini L, Porcu M, Pozzar F et al. A low pulse pressure is an independent predictor of mortality in heart failure: data from a large nationwide cardiology database (IN-CHF Registry). Ital Heart J 2004; 5: 892–898. 6 Jackson CE, Castagno D, Maggioni AP, Køber L, Squire IB, Swedberg K et al. Differing prognostic value of pulse pressure in patients with heart failure with reduced or preserved ejection fraction: results from the MAGGIC individual patient meta-analysis. Eur Heart J 2015; 36: 1106–1114.
Journal of Human Hypertension (2016) 293 – 294
7 Theilade S, Claggett B, Hansen TW, Skali H, Lewis EF, Solomonet SD et al. Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anaemia - the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT). J Hum Hypertens 2016; 30: 46–52. 8 Weber T, Wassertheurer S, Rammer M, Haiden A, Hametner B, Eber B. Wave reflections, assessed with a novel method for pulse wave separation, are associated with end-organ damage and clinical outcomes. Hypertension 2012; 60: 534–541. 9 Choi CU, Kim EJ, Kim SH, Shin SY, Choi UJ, Kim JW et al. Differing effects of aging on central and peripheral blood pressures and pulse wave velocity: a direct intraarterial study. J Hypertens 2010; 28: 1252–1260. 10 Weber T, Auer J, O’Rourke MF, Kvas E, Lassnig E, Berent R et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation 2004; 109: 184–189. 11 Westerhof N, O’Rourke MF. Haemodynamic basis for the development of the left ventricular failure in systolic hypertension and for its logical therapy. J Hypertens 1995; 13: 943–952. 12 Weber T, Auer J, Lamm G, O´Rourke MF, Eber B. Arterial stiffness, central blood pressure, and wave reflections in cardiomyopathy – implications for risk stratification. J Card Fail 2007; 13: 353–359. 13 Regnault V, Lagrange J, Pizard A, Safar ME, Fay R, Pitt B et al. Opposite predictive value of pulse pressure and aortic pulse wave velocity on heart failure with reduced left ventricular ejection fraction: insights from an eplerenone post–acute myocardial infarction heart failure efficacy and survival study (EPHESUS) substudy. Hypertension 2014; 63: 105–111. 14 Jankowski P, Kawecka-Jaszcz K, Czarnecka D, Brzozowska-Kiszka M, Styczkiewicz K, Loster M et al. Pulsatile but not steady component of blood pressure predicts cardiovascular events in coronary patients. Hypertension 2008; 51: 848–855. 15 Jankowski P, Blacher J, Weber T. In: Arterial stiffness, central blood pressure and coronary heart disease. Safar ME, O'Rourke MF, Frohlich ED (eds). Blood Pressure and Arterial Wall Mechanics in Cardiovascular Diseases. Springer: London, UK, 2014; 363–374.
© 2016 Macmillan Publishers Limited
