Ana Kadkhodayan1,2, C Huie Lin3,4, Andrew R Coggan5, Zulfia Kisrieva-Ware5, Kenneth B Schechtman6, Eric Novak3, Susan M Joseph3, Víctor G Dávila-Román3, Robert J Gropler5, Carmen Dence5, Linda R Peterson7. 1. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. 2. Cardiovascular Division, Department of Medicine, Mayo Clinic, Rochester, MN, USA. 3. Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, St. Louis, MO, 63110, USA. 4. Debakey Cardiovascular Associates, Houston Methodist Hospital, Houston, USA. 5. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA. 6. Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA. 7. Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Campus Box 8086, 660 S. Euclid Ave, St. Louis, MO, 63110, USA. lpeterso@DOM.wustl.edu.
Abstract
BACKGROUND: In animal models of heart failure (HF), myocardial metabolism shifts from high-energy fatty acid (FA) metabolism toward glucose. However, FA (vs glucose) metabolism generates more ATP/mole; thus, FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. METHODS AND RESULTS: We studied 19 well-matched men and women with nonischemic HF (EF ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/minute), FA uptake (mL/g/minute), and FA utilization (nmol/g/minute) (P < 0.005, P < 0.005, P < 0.05, respectively) and trended toward having higher FA oxidation than men (P = 0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. Higher MBF was related to improved event-free survival (HR 0.31, P = 0.02). CONCLUSIONS: In nonischemic HF, women have higher MBF and FA uptake and metabolism than men, irrespective of age, obesity, or insulin resistance. Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating MBF and metabolism in HF.
BACKGROUND: In animal models of heart failure (HF), myocardial metabolism shifts from high-energy fatty acid (FA) metabolism toward glucose. However, FA (vs glucose) metabolism generates more ATP/mole; thus, FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. METHODS AND RESULTS: We studied 19 well-matched men and women with nonischemic HF (EF ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/minute), FA uptake (mL/g/minute), and FA utilization (nmol/g/minute) (P < 0.005, P < 0.005, P < 0.05, respectively) and trended toward having higher FA oxidation than men (P = 0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. Higher MBF was related to improved event-free survival (HR 0.31, P = 0.02). CONCLUSIONS: In nonischemic HF, women have higher MBF and FA uptake and metabolism than men, irrespective of age, obesity, or insulin resistance. Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating MBF and metabolism in HF.
Authors: G de Simone; R B Devereux; S R Daniels; G Mureddu; M J Roman; T R Kimball; R Greco; S Witt; F Contaldo Journal: Circulation Date: 1997-04-01 Impact factor: 29.690
Authors: Linda R Peterson; Pablo F Soto; Pilar Herrero; B Selma Mohammed; Michael S Avidan; Kenneth B Schechtman; Carmen Dence; Robert J Gropler Journal: JACC Cardiovasc Imaging Date: 2008-07
Authors: Danilo Neglia; Alberto De Caterina; Paolo Marraccini; Andrea Natali; Marco Ciardetti; Cecilia Vecoli; Amalia Gastaldelli; Demetrio Ciociaro; Paola Pellegrini; Roberto Testa; Luca Menichetti; Antonio L'Abbate; William C Stanley; Fabio A Recchia Journal: Am J Physiol Heart Circ Physiol Date: 2007-10-05 Impact factor: 4.733
Authors: Pilar Herrero; Joonyoung Kim; Terry L Sharp; John A Engelbach; Jason S Lewis; Robert J Gropler; Michael J Welch Journal: J Nucl Med Date: 2006-03 Impact factor: 10.057
Authors: Pilar Herrero; Zulfia Kisrieva-Ware; Carmen S Dence; Bruce Patterson; Andrew R Coggan; Dong-Ho Han; Yosuke Ishii; Paul Eisenbeis; Robert J Gropler Journal: J Nucl Med Date: 2007-06 Impact factor: 10.057
Authors: Bente Kiens; Carsten Roepstorff; Jan F C Glatz; Arend Bonen; Peter Schjerling; Jens Knudsen; Jakob N Nielsen Journal: J Appl Physiol (1985) Date: 2004-05-21
Authors: T Rajendra Kumar; Jane E B Reusch; Wendy M Kohrt; Judith G Regensteiner Journal: J Womens Health (Larchmt) Date: 2020-05-17 Impact factor: 2.681
Authors: Kieren J Mather; Robert V Considine; LaTonya Hamilton; Niral A Patel; Carla Mathias; Wendy Territo; Adam G Goodwill; Johnathan D Tune; Mark A Green; Gary D Hutchins Journal: J Clin Endocrinol Metab Date: 2018-09-01 Impact factor: 5.958
Authors: Layla A Abushamat; P Mason McClatchey; Rebecca L Scalzo; Irene Schauer; Amy G Huebschmann; Kristen J Nadeau; Zhenqi Liu; Judith G Regensteiner; Jane E B Reusch Journal: J Endocr Soc Date: 2020-06-07
Authors: Manu S Goyal; Tyler M Blazey; Yi Su; Lars E Couture; Tony J Durbin; Randall J Bateman; Tammie L-S Benzinger; John C Morris; Marcus E Raichle; Andrei G Vlassenko Journal: Proc Natl Acad Sci U S A Date: 2019-02-04 Impact factor: 11.205