Assessment of Arterial Elastance and Ventricular-Arterial Coupling in Patients with Systemic Lupus Erythematosus (2014)

Patients with systemic lupus erythematosus (SLE) are at increased risk of premature atherosclerosis, mediated by endothelial dysfunction and increased arterial stiffness [[1]Chin C. Tan R.S. Thumboo J. Endothelial function and arterial stiffness assessment as early surrogate markers of vascular risk in patients with systemic lupus erythematosus.Clin Exp Rheumatol. 2013; 31: 295-301PubMed Google Scholar]. The latter, most commonly assessed using carotid-femoral pulse wave velocity, is increased in patients with SLE and is associated with cardiovascular risk factors [[1]Chin C. Tan R.S. Thumboo J. Endothelial function and arterial stiffness assessment as early surrogate markers of vascular risk in patients with systemic lupus erythematosus.Clin Exp Rheumatol. 2013; 31: 295-301PubMed Google Scholar]. Recently, a more sensitive measure of arterial stiffness (effective arterial elastance; Ea), and ventricular-arterial coupling (ratio of arterial and end-systolic ventricular elastance; Ea/Ees) demonstrated incremental prognostic value in patients with chronic heart failure [[2]Ky B. French B. Khan A.M. et al.Ventricular-Arterial Coupling, Remodeling, and Prognosis in Chronic Heart Failure.J Am Coll Cardiol. 2013; 62: 1165-1172Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar]. We aimed to assess the potential of Ea and Ea/Ees as novel biomarkers of cardiovascular risk in SLE women without ischemic heart disease. Women who satisfied the revised American College of Rheumatology classification criteria for SLE were prospectively recruited from the rheumatology clinics, as described previously [[3]Chin C. Chin C.Y. Ng M.X.R. et al.Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus.Rheumatol Int. Feb 19 2014; https://doi.org/10.1007/s00296-014-2968-4Crossref PubMed Scopus (15) Google Scholar]. Patients with recent active flares, ischemic heart disease (all patients underwent nuclear stress perfusion imaging as part of the study), cardiomyopathies (including myocarditis) and valvular heart disease of ≥ moderate severity were excluded. Cardiovascular risk was defined as history of hypertension, hyperlipidemia, diabetes mellitus, current tobacco use, cerebrovascular events, family history of coronary artery disease and secondary anti-phospholipid syndrome. Age-matched control women were recruited from the community. Left ventricular mass, diastolic function and systolic ejection fraction were assessed with echocardiography; Ea was estimated as 0.9 x (arm-cuff systolic pressure/Doppler stroke volume) and Ees was calculated by the well-validated approach of using arm-cuff pressures, Doppler stroke volumes, ejection fraction, pre-ejection and systolic periods [4Kelly R.P. Ting C.T. Yang T.M. et al.Effective arterial elastance as index of arterial vascular load in humans.Circulation. 1992; 86: 513-521Crossref PubMed Scopus (638) Google Scholar, 5Chen C.H. Fetics B. Nevo E. et al.Noninvasive single-beat determination of left ventricular end-systolic elastance in humans.J Am Coll Cardiol. 2001; 38: 2028-2034Abstract Full Text Full Text PDF PubMed Scopus (439) Google Scholar]. The study was conducted in accordance with the Declaration of Helsinki and approved by the local research ethics committee. Written informed consent was obtained from all participants. Continuous variables were presented in mean±SD or median [interquartile range] and compared using either the Student t test or Mann-Whitney U test, as appropriate. The mean differences in Ea and Ea/Ees were adjusted for age, systolic ejection fraction and systolic blood pressure. We assessed associations using the Pearson (r) or Spearman (ρ) correlation, as appropriate. All statistical analyses were performed with the SPSS version 19 (SPSS Inc, Chicago, USA). A two-sided P <0.05 was considered statistically significant. Forty-eight patients with SLE (43±9 years old; disease duration of 14±6 years; 1 [0,2] risk factors) and 20 control women (42±9 years old) were recruited. There were no differences in left ventricular mass, diastolic function and Ees between SLE and control women (P>0.50 for all; Table 1). Compared to control individuals, patients with SLE had lower systolic ejection fraction, albeit a small difference (71±8 versus 75±7%; P=0.04). Despite similar systolic blood pressure compared with control women (116±12 versus 119±16 mmHg; P=0.52), patients with SLE had increased Ea (1.77±0.56 versus 1.37±0.27 mmHg/mL; adjusted mean difference 0.30 mmHg/mL, 95% confidence interval [CI] 0.08 to 0.53 mmHg/mL, P<0.001) and Ea/Ees (0.61±0.18 versus 0.50±0.07; adjusted mean difference 0.06, 95% CI 0.01 to 0.12, P=0.04). Furthermore, Ea was associated with increasing cardiovascular risk (ρ=0.35; P=0.02), systolic blood pressure (r=0.55, P<0.001) and duration of prednisolone use (ρ=0.33, P=0.03).Table 1Characteristics of control individuals and patients with systemic lupus erythematosus (SLE).Control Individuals(n = 20)Patients with SLE(n = 48)P valueClinical characteristicAge, years42±943±90.71History of hypertension1 (5)12 (25)0.06History of diabetes mellitus02 (4)0.35History of hyperlipidemia010 (21)0.03Current tobacco use1 (5)4 (8)0.63Family history of coronary artery disease5 (25)7 (15)0.30History of cerebrovascular event07 (15)0.07Presence of secondary anti-phosphoplipid syndrome-12 (25)-Duration of SLE diagnosed, years-14±6-SLICC/ACR damage index¶SLICC/ACR Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index assessed organ damage in 12 systems with a maximum score of 47.-0 [0,1]-Current prednisolone use-25 (52)-Body mass index, kg/m223.8±3.723.4±5.00.76Systolic blood pressure, mmHg116±12119±160.52Low density lipoprotein cholesterol, mmol/L-3.0±0.7-High density lipoprotein cholesterol, mmol/L-1.3±0.4-Echocardiographic characteristicsIndexed left ventricular mass, g/m257 [52.72]60 [52,77]0.46Diastolic function E/e’6.9 [5.7,8.0]6.2 [4.9,8.3]0.48Systolic ejection fraction, %75±771±80.04Effective arterial elastance (Ea), mmHg/mL1.34 [1.25,1.49]1.64 [1.42,1.95]<0.001End-systolic elastance (Ees), mmHg/mL2.82 [2.36,3.19]3.03 [2.59,3.49]0.18Ea/Ees0.49 [0.45,0.55]0.56 [0.51,0.64]<0.001Results are presented in mean±SD, median [25th, 75th percentiles] or n (%).¶ SLICC/ACR Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index assessed organ damage in 12 systems with a maximum score of 47. Open table in a new tab Results are presented in mean±SD, median [25th, 75th percentiles] or n (%). Over 3 years of follow-up (median 31 [17,37] months), 8% of patients with SLE developed cardiovascular events (event rate 3.2 per 100 person-years; non-fatal myocardial infarction, n=2; stroke, n=1; significant coronary artery disease, n=1). Importantly, compared to control individuals and patients without events, SLE patients with cardiovascular events had increased Ea (1.33 [1.25,1.49] versus 1.59 [1.40,1.93] versus 2.10 [1.59,2.98] mmHg/mL, respectively; P<0.001) and Ea/Ees (0.49 [0.45,0.55] versus 0.55 [0.51,0.64] versus 0.59 [0.55,1.15], respectively; P<0.01). By design, we had excluded patients with ischemic heart disease and cardiomyopathies, as the role of non-invasive vascular imaging will be of greater relevance in these patients. Therefore, it was not surprising that we did not see any difference in Ees, a marker of ventricular stiffness, between SLE and control women. This was also supported by the similar left ventricular mass and diastolic function between SLE and control women. The small difference in systolic ejection fraction was likely an event of chance and not of important clinical significance. Conversely, Ea was significantly increased in patients with SLE compared to control women despite similar and normal blood pressures. The combination of these changes account for the small magnitude of Ea/Ees effect sizes. The association between Ea, Ea/Ees and adverse events is promising but we acknowledge this is exploratory and will require further validation in larger cohorts with longer follow-up. In conclusion, arterial elastance and ventricular-arterial coupling are associated with increased cardiovascular risk and are potential novel markers of adverse cardiovascular events in patients with SLE. The authors report no relationships that could be construed as a conflict of interest