Sex Differences in Cardiometabolic Traits and Determinants of Exercise Capacity in Heart Failure With Preserved Ejection Fraction.

Lau ES, Cunningham T, Hardin KM, Liu E, Malhotra R, Nayor M, Lewis GD, Ho JE

JAMA Cardiol. 2019 Oct 30. doi: 10.1001/jamacardio.2019.4150. [Epub ahead of

Importance: Sex differences in heart failure with preserved ejection fraction
(HFpEF) have been established, but insights into the mechanistic drivers of these
differences are limited.
Objective: To examine sex differences in cardiometabolic profiles and exercise
hemodynamic profiles among individuals with HFpEF.
Design, Setting, and Participants: This cross-sectional study was conducted at a
single-center tertiary care referral hospital from December 2006 to June 2017 and
included 295 participants who met hemodynamic criteria for HFpEF based on
invasive cardiopulmonary exercise testing results. We examined sex differences in
distinct components of oxygen transport and utilization during exercise using
linear and logistic regression models. The data were analyzed from June 2018 to
May 2019.
Main Outcomes and Measures: Resting and exercise gas exchange and hemodynamic
parameters obtained during cardiopulmonary exercise testing.
Results: Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years)
and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men,
women with HFpEF in this tertiary referral cohort had fewer comorbidities,
including diabetes, insulin resistance, and hypertension, and a more favorable
adipokine profile. Exercise capacity was similar in men and women (percent
predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but
women had distinct deficits in components of the O2 pathway, including worse
biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70;
SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve
(PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2
β=-0.90, SE=0.22; P < .001)).
Conclusions and Relevance: Despite a lower burden of cardiometabolic disease and
a similar percent predicted exercise capacity, women with HFpEF demonstrated
greater cardiac and extracardiac deficits, including systolic reserve, diastolic
reserve, and peripheral O2 extraction. These sex differences in cardiac and
skeletal muscle responses to exercise may illuminate the pathophysiology
underlying the development of HFpEF and should be investigated further.