How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial

被引:93
作者
Bosch, Agnes [1 ]
Ott, Christian [1 ,2 ]
Jung, Susanne [3 ]
Striepe, Kristina [1 ]
Karg, Marina V. [1 ]
Kannenkeril, Dennis [1 ]
Dienemann, Thomas [1 ]
Schmieder, Roland E. [1 ]
机构
[1] Friedrich Alexander Univ Erlangen Nurnberg FAU, Dept Hypertens & Nephrol, Erlangen, Germany
[2] Paracelsus Med Sch Nurnberg, Nurnberg, Germany
[3] Friedrich Alexander Univ Erlangen Nurnberg FAU, Dept Cardiol, Erlangen, Germany
关键词
Diabetes mellitus type 2; Empagliflozin; Vascular function; Central hemodynamics; Inflammation; COTRANSPORTER; 2; INHIBITOR; BLOOD-PRESSURE; POTENTIAL MECHANISMS; CENTRAL HEMODYNAMICS; CARDIOVASCULAR RISK; SGLT2; INHIBITION; PULSE PRESSURE; DAPAGLIFLOZIN; DISEASE; CANAGLIFLOZIN;
D O I
10.1186/s12933-019-0839-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundEmpagliflozin has been shown to reduce cardiovascular mortality, but the underlying pathogenetic mechanisms are poorly understood. It was previously demonstrated that empagliflozin improved arterial stiffness.MethodsOur analysis comprising 58 patients with type 2 diabetes mellitus identifies factors triggering the improvement of arterial stiffness. All patients participated in an investigator-initiated, prospective, double-blind, randomized, placebo-controlled, interventional clinical trial (http://www.ClinicalTrials.gov: NCT02471963, registered 15th June 2015, retrospectively registered) and received either 6-weeks treatment with 25mg empagliflozin orally once daily or placebo (crossover). Central systolic pressure and central pulse pressure were recorded by the SphygmoCor System (AtCor Medical). Now, we investigated the impact of parameters of glucose metabolism, volume status, sympathetic activation, lipids, uric acid, blood pressure and inflammation on vascular parameters of arterial stiffness using multivariate regression analysis.ResultsAs previously reported, therapy with empagliflozin improved arterial stiffness as indicated by reduced central systolic blood pressure (113.612.1 vs 118.612.9mmHg, p<0.001), central pulse pressure (39.1 +/- 10.2 vs 41.9 +/- 10.7mmHg, p=0.027) forward (27.1 +/- 5.69 vs 28.7 +/- 6.23mmHg, p=0.031) as well as reflected wave amplitude (18.9 +/- 5.98 vs 20.3 +/- 5.97mmHg, p=0.045) compared to placebo. The multivariate regression analysis included age, sex and change between empagliflozin and placebo therapy of the following parameters: HbA1c, copeptin, hematocrit, heart rate, LDL-cholesterol, uric acid, systolic 24-h ambulatory blood pressure and high sensitive CRP (hsCRP). Besides the influence of age (beta=-0.259, p=0.054), sex (beta=0.292, p=0.040) and change in systolic 24-h ambulatory blood pressure (beta=0.364, p=0.019), the change of hsCRP (beta=0.305, p=0.033) emerged as a significant determinant of the empagliflozin induced reduction in arterial stiffness (placebo corrected). When replacing HbA1c with fasting plasma glucose in the multivariate regression analysis, a similar effect of the change in hsCRP (beta=0.347, p=0.017) on arterial stiffness parameters was found.Conclusion Besides age and sex, change in systolic 24-h ambulatory blood pressure and change in hsCRP were determinants of the empagliflozin induced improvement of vascular parameters of arterial stiffness, whereas parameters of change in glucose metabolism and volume status had no significant influence. Our analysis suggests that empagliflozin exerts, at least to some extent, its beneficial vascular effects via anti-inflammatory mechanisms.
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页数:12
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共 42 条
  • [1] Assessment of Textural Differentiations in Forest Resources in Romania Using Fractal Analysis
    Andronache, Ion
    Fensholt, Rasmus
    Ahammer, Helmut
    Ciobotaru, Ana-Maria
    Pintilii, Radu-Daniel
    Peptenatu, Daniel
    Draghici, Cristian-Constantin
    Diaconu, Daniel Constantin
    Radulovic, Marko
    Pulighe, Giuseppe
    Azihou, Akomian Fortune
    Toyi, Mireille Scholastique
    Sinsin, Brice
    [J]. FORESTS, 2017, 8 (03):
  • [2] Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury
    Aroor, Annayya R.
    Das, Nitin A.
    Carpenter, Andrea J.
    Habibi, Javad
    Jia, Guanghong
    Ramirez-Perez, Francisco I.
    Martinez-Lemus, Luis
    Manrique-Acevedo, Camila M.
    Hayden, Melvin R.
    Duta, Cornel
    Nistala, Ravi
    Mayoux, Eric
    Padilla, Jaume
    Chandrasekar, Bysani
    DeMarco, Vincent G.
    [J]. CARDIOVASCULAR DIABETOLOGY, 2018, 17
  • [3] Bekki M, 2018, CURR VASC PHARM
  • [4] Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism
    Briand, Francois
    Mayoux, Eric
    Brousseau, Emmanuel
    Burr, Noemie
    Urbain, Isabelle
    Costard, Clement
    Mark, Michael
    Sulpice, Thierry
    [J]. DIABETES, 2016, 65 (07) : 2032 - 2038
  • [5] Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes
    Chilton, R.
    Tikkanen, I.
    Cannon, C. P.
    Crowe, S.
    Woerle, H. J.
    Broedl, U. C.
    Johansen, O. E.
    [J]. DIABETES OBESITY & METABOLISM, 2015, 17 (12) : 1180 - 1193
  • [6] Comparison of an Oscillometric Method with Cardiac Magnetic Resonance for the Analysis of Aortic Pulse Wave Velocity
    Feistritzer, Hans-Josef
    Reinstadler, Sebastian J.
    Klug, Gert
    Kremser, Christian
    Seidner, Benjamin
    Esterhammer, Regina
    Schocke, Michael F.
    Franz, Wolfgang-Michael
    Metzler, Bernhard
    [J]. PLOS ONE, 2015, 10 (01):
  • [7] Renal Handling of Ketones in Response to Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes
    Ferrannini, Ele
    Baldi, Simona
    Frascerra, Silvia
    Astiarraga, Brenno
    Barsotti, Elisabetta
    Clerico, Aldo
    Muscelli, Elza
    [J]. DIABETES CARE, 2017, 40 (06) : 771 - 776
  • [8] Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial
    Fitchett, David
    Zinman, Bernard
    Wanner, Christoph
    Lachin, John M.
    Hantel, Stefan
    Salsali, Afshin
    Johansen, Odd Erik
    Woerle, Hans J.
    Broedl, Uli C.
    Inzucchi, Silvio E.
    Aizenberg, D.
    Ulla, M.
    Waitman, J.
    De Loredo, L.
    Farias, J.
    Fideleff, H.
    Lagrutta, M.
    Maldonado, N.
    Colombo, H.
    Ferre Pacora, F.
    Wasserman, A.
    Maffei, L.
    Lehman, R.
    Selvanayagam, J.
    d'Emden, M.
    Fasching, P.
    Paulweber, B.
    Toplak, H.
    Luger, A.
    Drexel, H.
    Prager, R.
    Schnack, C.
    Schernthaner, G.
    Fliesser-Goerzer, E.
    Kaser, S.
    Scheen, A.
    Van Gaal, L.
    Hollanders, G.
    Kockaerts, Y.
    Capiau, L.
    Chachati, A.
    Persu, A.
    Hermans, M.
    Vantroyen, D.
    Vercammen, C.
    Van de Borne, P.
    Mathieu, C.
    Benhalima, K.
    Lienart, F.
    Mortelmans, J.
    [J]. EUROPEAN HEART JOURNAL, 2016, 37 (19) : 1526 - 1534
  • [9] Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes
    Gaede, P
    Vedel, P
    Larsen, N
    Jensen, GVH
    Parving, H
    Pedersen, O
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (05) : 383 - 393
  • [10] Oscillometric estimation of aortic pulse wave velocity: comparison with intra-aortic catheter measurements
    Hametner, Bernhard
    Wassertheurer, Siegfried
    Kropf, Johannes
    Mayer, Christopher
    Eber, Bernd
    Weber, Thomas
    [J]. BLOOD PRESSURE MONITORING, 2013, 18 (03) : 173 - 176